NM_000059.4(BRCA2):c.9907A>T (p.Ser3303Cys) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 1, 2023
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:: RCV000112821.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.9907A>T (p.Ser3303Cys)]

NM_000059.4(BRCA2):c.9907A>T (p.Ser3303Cys)

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.9907A>T (p.Ser3303Cys)

HGVS:

NC_000013.11:g.32398420A>T
NG_012772.3:g.87941A>T
NM_000059.4:c.9907A>TMANE SELECT
NP_000050.2:p.Ser3303Cys
NP_000050.3:p.Ser3303Cys
LRG_293t1:c.9907A>T
LRG_293:g.87941A>T
LRG_293p1:p.Ser3303Cys
NC_000013.10:g.32972557A>T
NM_000059.3:c.9907A>T
U43746.1:n.10135A>T
p.S3303C

Protein change:

S3303C

Links:

dbSNP: rs276174930

NCBI 1000 Genomes Browser:

rs276174930

Molecular consequence:

NM_000059.4:c.9907A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:: Breast-ovarian cancer, familial 2
Identifiers:: MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000145728	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Uncertain significance (Sep 18, 2010)	germline	clinical testing
SCV004846246	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Dec 1, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18627636, 33314489, 33471991, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000145728

Breast Cancer Information Core (BIC) (BRCA2)

no assertion criteria provided

Uncertain significance
(Sep 18, 2010)

germline

clinical testing

SCV004846246

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Dec 1, 2023)

germline

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	unknown	2	not provided	not provided	108544	not provided	clinical testing
Indian, Malay	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer.

Thirthagiri E, Lee SY, Kang P, Lee DS, Toh GT, Selamat S, Yoon SY, Taib NA, Thong MK, Yip CH, Teo SH.

Breast Cancer Res. 2008;10(4):R59. doi: 10.1186/bcr2118. Epub 2008 Jul 16.

PubMed [citation]

PMID:: 18627636
PMCID:: PMC2575532

Epidemiological and ES cell-based functional evaluation of BRCA2 variants identified in families with breast cancer.

Sullivan T, Thirthagiri E, Chong CE, Stauffer S, Reid S, Southon E, Hassan T, Ravichandran A, Wijaya E, Lim J, Taib NAM, Fadzli F, Yip CH, Hartman M, Li J, van Dam RM, North SL, Das R, Easton DF, Biswas K, Teo SH, Sharan SK; et al.

Hum Mutat. 2021 Feb;42(2):200-212. doi: 10.1002/humu.24154. Epub 2020 Dec 31.

PubMed [citation]

PMID:: 33314489
PMCID:: PMC7919386

See all PubMed Citations (4)

Details of each submission

From Breast Cancer Information Core (BIC) (BRCA2), SCV000145728.1

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

#	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		1	not provided	not provided	not provided

From All of Us Research Program, National Institutes of Health, SCV004846246.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

Description

This missense variant replaces serine with cysteine at codon 3303 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A functional study in mouse embryonic stem cells has shown this variant does not impact sensitivity to DNA damaging agents (PMID: 33314489). This variant has been reported in at least one individual affected with breast cancer (PMID: 18627636, 33471991; Leiden Open Variation Database DB-ID BRCA2_003783). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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