NM_000059.4(BRCA2):c.8175del (p.Trp2725fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 28, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004524741.1

Allele description [Variation Report for NM_000059.4(BRCA2):c.8175del (p.Trp2725fs)]

NM_000059.4(BRCA2):c.8175del (p.Trp2725fs)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.8175del (p.Trp2725fs)

HGVS:

NC_000013.11:g.32363377del
NG_012772.3:g.52898del
NM_000059.3:c.8175delG
NM_000059.4:c.8175delMANE SELECT
NP_000050.3:p.Trp2725fs
LRG_293t1:c.8175del
LRG_293:g.52898del
NC_000013.10:g.32937514del

Protein change:

W2725fs

Molecular consequence:

NM_000059.4:c.8175del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005030655	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 28, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25186627, 29486991 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005030655

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 28, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]

PMID:: 25186627

Characteristics of African American women at high-risk for ovarian cancer in the southeast: Results from a Gynecologic Cancer Risk Assessment Clinic.

Barrington DA, Champion ML, Boitano TKL, Walters-Haygood CL, Farmer MB, Alvarez RD, Estes JM, Leath CA 3rd.

Gynecol Oncol. 2018 May;149(2):337-340. doi: 10.1016/j.ygyno.2018.02.014. Epub 2018 Mar 2.

PubMed [citation]

PMID:: 29486991
PMCID:: PMC5915908

Details of each submission

From Ambry Genetics, SCV005030655.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.8175delG pathogenic mutation, located in coding exon 17 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 8175, causing a translational frameshift with a predicted alternate stop codon (p.W2725Cfs*8). This alteration was identified in 2 of 66 African American women undergoing genetic testing based on a personal and/or family history of breast, ovarian, and/or other gynecologic cancer (Barrington DA et al. Gynecol Oncol, 2018 May;149:337-340). This variant was also observed in an individual with early onset-breast cancer amongst a cohort of 1781 non-Ashkenazi Jewish individuals undergoing BRCA1/2 gene testing based on a personal history of breast cancer (Tung N et al. Cancer, 2015 Jan;121:25-33). Of note, this alteration is also known as 8403delG in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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