VCV000221152.41 - ClinVar

NM_002691.4(POLD1):c.778A>G (p.Ile260Val)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(15)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(8); Likely benign(4)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002691.4(POLD1):c.778A>G (p.Ile260Val)

Variation ID: 221152 Accession: VCV000221152.41

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19q13.33 19: 50402473 (GRCh38) [ NCBI UCSC ] 19: 50905730 (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	Sep 28, 2017	Oct 20, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_002691.4:c.778A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002682.2:p.Ile260Val	missense
NM_001256849.1:c.778A>G	NP_001243778.1:p.Ile260Val	missense
NM_001308632.1:c.778A>G	NP_001295561.1:p.Ile260Val	missense
NR_046402.2:n.823A>G		non-coding transcript variant
NC_000019.10:g.50402473A>G
NC_000019.9:g.50905730A>G
NG_033800.1:g.23151A>G
LRG_785:g.23151A>G
LRG_785t1:c.778A>G	LRG_785p1:p.Ile260Val
LRG_785t2:c.778A>G	LRG_785p2:p.Ile260Val

... more HGVS ... less HGVS

Protein change

I260V

Other names

Canonical SPDI

NC_000019.10:50402472:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00240 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00069

Exome Aggregation Consortium (ExAC) 0.00098

1000 Genomes Project 0.00240

1000 Genomes Project 30x 0.00250

The Genome Aggregation Database (gnomAD) 0.00295

Trans-Omics for Precision Medicine (TOPMed) 0.00304

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00308

Links

ClinGen: CA349220 dbSNP: rs8105725 VarSome

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
Gene	OMIM	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.
POLD1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	4946	4996

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.
not specified	Conflicting interpretations of pathogenicity (4)	criteria provided, conflicting classifications	Aug 15, 2023	RCV000213915.22
Hereditary cancer-predisposing syndrome	Benign (3)	criteria provided, multiple submitters, no conflicts	Mar 1, 2020	RCV000568363.11
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Apr 1, 2022	RCV000759964.30
Colorectal cancer, susceptibility to, 10	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV001084127.17
Colorectal cancer, susceptibility to, 10 Mandibular hypoplasia-deafness-progeroid syndrome	Likely benign (1)	criteria provided, single submitter	Aug 10, 2021	RCV002485354.8
POLD1-related disorder	Benign (1)	no assertion criteria provided	Mar 1, 2019	RCV004530248.2

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.
Likely benign (Mar 12, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000279380.9 First in ClinVar: May 29, 2016 Last updated: Apr 09, 2018
Benign (May 22, 2021)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV002047914.1 First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022
Benign (Jan 18, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV002068326.1 First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022
Likely benign (Mar 04, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002500091.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022
Benign (Mar 01, 2020)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002534703.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Benign (Nov 14, 2017)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000889690.3 First in ClinVar: Mar 14, 2019 Last updated: Dec 31, 2022
Likely benign (Aug 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Colorectal cancer, susceptibility to, 10 Mandibular hypoplasia-deafness-progeroid syndrome Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002800318.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Colorectal cancer, susceptibility to, 10 Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004016620.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Uncertain significance (Aug 15, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV004026992.1 First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Colorectal cancer, susceptibility to, 10 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000262369.11 First in ClinVar: Feb 02, 2016 Last updated: Feb 28, 2024
Benign (Jun 05, 2015)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000670912.5 First in ClinVar: Jan 01, 2018 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)
Benign (Apr 01, 2022)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004140554.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: POLD1: BS1, BS2 Number of individuals with the variant: 1
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005205883.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (Oct 10, 2017)	no assertion criteria provided Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	True Health Diagnostics Accession: SCV000788151.1 First in ClinVar: Jan 01, 2018 Last updated: Jan 01, 2018
Benign (Mar 01, 2019)	no assertion criteria provided Method: clinical testing	POLD1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004729628.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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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.

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:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs8105725 ...

These 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 19, 2024

ClinVar Genomic variation as it relates to human health

NM_002691.4(POLD1):c.778A>G (p.Ile260Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs8105725 ...