Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.2552 (Asian), 0.09756 (African), 0.2876 (European), derived from 1000 genomes (2012-04-30).
ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.1114A>C (p.Asn372His)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Benign
Jan 2015 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000059.4(BRCA2):c.1114A>C (p.Asn372His)
Variation ID: 9329 Accession: VCV000009329.90
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q13.1 13: 32332592 (GRCh38) [ NCBI UCSC ] 13: 32906729 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 12, 2013 Sep 29, 2024 Jan 12, 2015 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000059.4:c.1114A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Asn372His missense NC_000013.11:g.32332592A>C NC_000013.10:g.32906729A>C NG_012772.3:g.22113A>C LRG_293:g.22113A>C LRG_293t1:c.1114A>C LRG_293p1:p.Asn372His NP_000050.2:p.Asn372His - Protein change
- N372H
- Other names
-
1342 A>C
NP_000050.3:p.Asn372His
- Canonical SPDI
- NC_000013.11:32332591:A:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.24940 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.23116
Trans-Omics for Precision Medicine (TOPMed) 0.23829
1000 Genomes Project 0.24940
1000 Genomes Project 30x 0.25016
Exome Aggregation Consortium (ExAC) 0.27793
The Genome Aggregation Database (gnomAD), exomes 0.27964
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18995 | 19154 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Benign (13) |
reviewed by expert panel
|
Jan 12, 2015 | RCV000009916.32 | |
| Benign (5) |
criteria provided, multiple submitters, no conflicts
|
Nov 29, 2023 | RCV000034427.30 | |
| Benign (9) |
criteria provided, multiple submitters, no conflicts
|
Nov 1, 2017 | RCV000120303.36 | |
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 17, 2020 | RCV000130720.15 | |
| Uncertain significance (1) |
no assertion criteria provided
|
Jul 20, 2015 | RCV000207052.9 | |
| Benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000260146.13 | |
| Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000320173.21 | |
| Benign (1) |
criteria provided, single submitter
|
Feb 23, 2017 | RCV000468776.9 | |
| Benign (1) |
criteria provided, single submitter
|
Apr 18, 2019 | RCV000768560.9 | |
| Benign (1) |
criteria provided, single submitter
|
Apr 29, 2022 | RCV002476952.8 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Jan 12, 2015)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial 2
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000245002.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Comment:
Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.2552 (Asian), 0.09756 (African), 0.2876 (European), derived from 1000 genomes (2012-04-30).
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000301752.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Nov 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000693629.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
|
|
Benign
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744401.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Benign
(Oct 23, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000202279.7
First in ClinVar: Jan 29, 2015 Last updated: Feb 19, 2018 |
Number of individuals with the variant: 206
Zygosity: Homozygote, Hemizygote, Single Heterozygote
Sex: mixed
|
|
|
Benign
(May 23, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966258.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
p.Asn372His in exon 10 of BRCA2: This variant is not expected to have clinical s ignificance because it has been identified in 35.58% (5867/16490) of … (more)
p.Asn372His in exon 10 of BRCA2: This variant is not expected to have clinical s ignificance because it has been identified in 35.58% (5867/16490) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs144848). (less)
Number of individuals with the variant: 1
|
|
|
Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001138988.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
|
|
|
Benign
(Jan 17, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002533208.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
|
Benign
(Jan 23, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000494300.2
First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022 |
|
|
|
Benign
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016805.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
|
|
Benign
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004846864.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 50019
Zygosity: Homozygote, Single Heterozygote
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005236034.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Nov 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000195957.1
First in ClinVar: Nov 14, 2015 Last updated: Nov 14, 2015 |
Tissue: Blood
|
|
|
Benign
(Nov 04, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000292084.1
First in ClinVar: Jul 08, 2016 Last updated: Jul 08, 2016 |
|
|
|
Benign
(Feb 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
germline
|
Baylor Genetics
Accession: SCV000541021.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
|
|
|
Benign
(Apr 18, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000586924.1 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
|
Benign
(Oct 09, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743255.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Benign
(Apr 18, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast carcinoma
Affected status: yes
Allele origin:
germline
|
Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Faculty of Medicine Ramathibodi Hospital, Mahidol University
Accession: SCV000899225.1
First in ClinVar: May 02, 2019 Last updated: May 02, 2019 |
Sex: female
|
|
|
Benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383627.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
|
|
|
Benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group D1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383626.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
|
|
|
Benign
(May 03, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
unknown
|
Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000746278.2
First in ClinVar: Apr 09, 2018 Last updated: May 31, 2020 |
|
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001887957.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 32846166, 25348552, 21476145, 24289560, 32356124, 31477031, 29988080, 21990134, 24728327, 26306726, 27153395, 11062481, 19253839, 18288416, 22044372, 24323938, … (more)
This variant is associated with the following publications: (PMID: 32846166, 25348552, 21476145, 24289560, 32356124, 31477031, 29988080, 21990134, 24728327, 26306726, 27153395, 11062481, 19253839, 18288416, 22044372, 24323938, 23249957, 14555511, 15695382, 21702907, 17767707, 21952622, 20352487, 20135345, 22703879) (less)
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: no
Allele origin:
germline
|
GreenArray Genomic Research & Solutions of Accurate Diagnostic Private Limited
Accession: SCV002097610.1
First in ClinVar: Feb 20, 2022 Last updated: Feb 20, 2022 |
Sex: female
|
|
|
Benign
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002026062.2
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 493
Geographic origin: South Africa
|
|
|
Benign
(Nov 01, 2021)
|
criteria provided, single submitter
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Genetics Program, Instituto Nacional de Cancer
Accession: SCV002515247.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Geographic origin: Brazil
|
|
|
Benign
(Jan 02, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000154058.2
First in ClinVar: Jun 04, 2014 Last updated: Dec 24, 2022 |
Comment:
High frequency in a 1kG or ESP population: 28.6 %.
|
|
|
Benign
(Apr 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Medulloblastoma Familial prostate cancer Wilms tumor 1 Fanconi anemia complementation group D1 Breast-ovarian cancer, familial, susceptibility to, 2 Glioma susceptibility 3 Pancreatic cancer, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000575730.2
First in ClinVar: Nov 14, 2015 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001000148.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Nov 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602750.10
First in ClinVar: Sep 28, 2017 Last updated: Feb 20, 2024 |
|
|
|
Benign
(May 07, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000185607.7
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
no known pathogenicity
(Jul 13, 2012)
|
no assertion criteria provided
Method: research
|
not provided
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043195.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Benign.
Number of individuals with the variant: 298
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
|
|
|
Uncertain significance
(Jul 20, 2015)
|
no assertion criteria provided
Method: research
|
Breast ductal adenocarcinoma
Male breast cancer
Affected status: yes
Allele origin:
germline
|
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.
Accession: SCV000258681.1
First in ClinVar: Feb 09, 2016 Last updated: Feb 09, 2016 |
Family history: no
Sex: male
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733222.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Uncertain significance
(Feb 01, 2014)
|
no assertion criteria provided
Method: literature only
|
RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000030137.5
First in ClinVar: Apr 04, 2013 Last updated: May 21, 2018 |
Comment on evidence:
This variant, formerly titled BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2, has been reclassified based on the findings of Guidugli et al. (2014). Healey et al. … (more)
This variant, formerly titled BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2, has been reclassified based on the findings of Guidugli et al. (2014). Healey et al. (2000) described a polymorphism of the BRCA2 gene, asn372 to his (N372H), located in exon 10 and associated not only with an increased risk of breast cancer (BROVCA2; 612555) but also with an effect on prenatal viability with increased fitness of males and decreased fitness of females. The rarer allele (372H) had a frequency of 0.221 in Finnish, 0.285 in German, and a frequency intermediate between these 2 in British populations. HH homozygotes were found to have a 1.31-fold (95% confidence interval, 1.07-1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there was a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there was an excess of homozygotes: the HH group had an estimated fitness of 0.82 in females and 1.38 in males. The authors suggested that the differences in genotype may be due to selection, and concluded that this variant of BRCA2 may also affect fetal survival in a sex-dependent manner. Using a mathematical model to analyze the BRCA2 N372H polymorphism data reported by Healey et al. (2000) as well as data from 8 other populations, Teare et al. (2004) found significant evidence consistent with a heterozygote advantage in females, but no evidence of genotype-specific selection in males. Functional assays used to assess the impact of the N372H variant indicated that N372H is a class 1 variant (not pathogenic or of no clinical significance), according to the International Agency for Research on Cancer (IARC) class system (Guidugli et al., 2014). (less)
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955060.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
|
Benign
(Nov 28, 2016)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000778640.1
First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001549425.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 3
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906288.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000084455.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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Comment:
Comment:
p.Asn372His in exon 10 of BRCA2: This variant is not expected to have clinical s ignificance because it has been identified in 35.58% (5867/16490) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs144848).
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Comment:
This variant is associated with the following publications: (PMID: 32846166, 25348552, 21476145, 24289560, 32356124, 31477031, 29988080, 21990134, 24728327, 26306726, 27153395, 11062481, 19253839, 18288416, 22044372, 24323938, 23249957, 14555511, 15695382, 21702907, 17767707, 21952622, 20352487, 20135345, 22703879)
Comment:
High frequency in a 1kG or ESP population: 28.6 %.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Converted during submission to Benign.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.2552 (Asian), 0.09756 (African), 0.2876 (European), derived from 1000 genomes (2012-04-30).
Comment:
p.Asn372His in exon 10 of BRCA2: This variant is not expected to have clinical s ignificance because it has been identified in 35.58% (5867/16490) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs144848).
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Comment:
This variant is associated with the following publications: (PMID: 32846166, 25348552, 21476145, 24289560, 32356124, 31477031, 29988080, 21990134, 24728327, 26306726, 27153395, 11062481, 19253839, 18288416, 22044372, 24323938, 23249957, 14555511, 15695382, 21702907, 17767707, 21952622, 20352487, 20135345, 22703879)
Comment:
High frequency in a 1kG or ESP population: 28.6 %.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Converted during submission to Benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service. | Matta BP | Scientific reports | 2022 | PMID: 36329109 |
| Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience. | Van der Merwe NC | Frontiers in genetics | 2022 | DOI: 10.3389/fgene.2022.834265 |
| Functional assays for analysis of variants of uncertain significance in BRCA2. | Guidugli L | Human mutation | 2014 | PMID: 24323938 |
| BRCA2 N372H polymorphism and breast cancer susceptibility: a meta-analysis involving 44,903 subjects. | Qiu LX | Breast cancer research and treatment | 2010 | PMID: 20135345 |
| Association between the BRCA2 N372H variant and male breast cancer risk: a population-based case-control study in Tuscany, Central Italy. | Palli D | BMC cancer | 2007 | PMID: 17767707 |
| Heterozygote excess is repeatedly observed in females at the BRCA2 locus N372H. | Teare MD | Journal of medical genetics | 2004 | PMID: 15235023 |
| Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer. | Wenham RM | Clinical cancer research : an official journal of the American Association for Cancer Research | 2003 | PMID: 14555511 |
| The BRCA2 372 HH genotype is associated with risk of breast cancer in Australian women under age 60 years. | Spurdle AB | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2002 | PMID: 11927503 |
| A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability. | Healey CS | Nature genetics | 2000 | PMID: 11062481 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 | - | - | - | - |
Text-mined citations for rs144848 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.