NM_000059.4(BRCA2):c.1600G>A (p.Glu534Lys) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Aug 8, 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:: RCV000031330.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.1600G>A (p.Glu534Lys)]

NM_000059.4(BRCA2):c.1600G>A (p.Glu534Lys)

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.1600G>A (p.Glu534Lys)

HGVS:

NC_000013.11:g.32333078G>A
NG_012772.3:g.22599G>A
NM_000059.4:c.1600G>AMANE SELECT
NP_000050.2:p.Glu534Lys
NP_000050.3:p.Glu534Lys
LRG_293t1:c.1600G>A
LRG_293:g.22599G>A
LRG_293p1:p.Glu534Lys
NC_000013.10:g.32907215G>A
NM_000059.3:c.1600G>A
U43746.1:n.1828G>A
p.E534K

Nucleotide change:

1828G>A

Protein change:

E534K

Links:

dbSNP: rs276174810

NCBI 1000 Genomes Browser:

rs276174810

Molecular consequence:

NM_000059.4:c.1600G>A - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000053935	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Uncertain significance (Jul 12, 2010)	germline	clinical testing
SCV000145896	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Uncertain significance (Sep 18, 2010)	germline	clinical testing
SCV000785626	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Oct 16, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf, Citation Link,
SCV004846939	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Aug 8, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18627636, 33314489, 33471991, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	108544	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Sharing Clinical Reports Project (SCRP), SCV000053935.3

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

From Breast Cancer Information Core (BIC) (BRCA2), SCV000145896.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	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 Counsyl, SCV000785626.2

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

#	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

From All of Us Research Program, National Institutes of Health, SCV004846939.1

#	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 glutamic acid with lysine at codon 534 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 has shown this variant does not impact cell viability or sensitivity to DNA-damaging agents (PMID: 33314489). This variant has been reported in at least two individuals affected with breast cancer and two unaffected individuals (PMID: 18627636, 33314489, 33471991; Leiden Open Variation Database DB-ID BRCA2_007646). This variant has been identified in 4/248706 chromosomes 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: Jun 2, 2024

ClinVar

Relating variation to medicine