NM_000059.4(BRCA2):c.8825C>T (p.Ala2942Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 6, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001775622.4

Allele description [Variation Report for NM_000059.4(BRCA2):c.8825C>T (p.Ala2942Val)]

NM_000059.4(BRCA2):c.8825C>T (p.Ala2942Val)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.8825C>T (p.Ala2942Val)

HGVS:

NC_000013.11:g.32379387C>T
NG_012772.3:g.68908C>T
NM_000059.4:c.8825C>TMANE SELECT
NP_000050.2:p.Ala2942Val
NP_000050.3:p.Ala2942Val
LRG_293t1:c.8825C>T
LRG_293:g.68908C>T
LRG_293p1:p.Ala2942Val
NC_000013.10:g.32953524C>T
NM_000059.3:c.8825C>T
p.A2942V

Protein change:

A2942V

Links:

dbSNP: rs373227180

NCBI 1000 Genomes Browser:

rs373227180

Molecular consequence:

NM_000059.4:c.8825C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002012889	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 6, 2023)	germline	clinical testing	Citation Link,
SCV004220630	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Nov 3, 2022)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 32068069, 31853058, 32256484, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002012889

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 6, 2023)

germline

clinical testing

Citation Link,

SCV004220630

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Nov 3, 2022)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Germline Mutation in 1338 BRCA-Negative Chinese Hereditary Breast and/or Ovarian Cancer Patients: Clinical Testing with a Multigene Test Panel.

Kwong A, Shin VY, Chen J, Cheuk IWY, Ho CYS, Au CH, Chan KKL, Ngan HYS, Chan TL, Ford JM, Ma ESK.

J Mol Diagn. 2020 Apr;22(4):544-554. doi: 10.1016/j.jmoldx.2020.01.013. Epub 2020 Feb 15.

PubMed [citation]

PMID:: 32068069

Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort.

Li H, LaDuca H, Pesaran T, Chao EC, Dolinsky JS, Parsons M, Spurdle AB, Polley EC, Shimelis H, Hart SN, Hu C, Couch FJ, Goldgar DE.

Genet Med. 2020 Apr;22(4):701-708. doi: 10.1038/s41436-019-0729-1. Epub 2019 Dec 19.

PubMed [citation]

PMID:: 31853058
PMCID:: PMC7118020

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV002012889.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 9053C>T; This variant is associated with the following publications: (PMID: 34741701, 29884841, 12228710, 30877237, 32377563, 32068069, 34250417)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220630.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The frequency of this variant in the general population, 0.0000066 (1/152080 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual affected with breast/ovarian cancer (PMID: 32068069 (2020)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Nov 3, 2024

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