NM_000059.4(BRCA2):c.461A>G (p.Gln154Arg) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 29, 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:: RCV001853356.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.461A>G (p.Gln154Arg)]

NM_000059.4(BRCA2):c.461A>G (p.Gln154Arg)

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.461A>G (p.Gln154Arg)

HGVS:

NC_000013.11:g.32326136A>G
NG_012772.3:g.15657A>G
NM_000059.4:c.461A>GMANE SELECT
NP_000050.2:p.Gln154Arg
NP_000050.3:p.Gln154Arg
LRG_293t1:c.461A>G
LRG_293:g.15657A>G
LRG_293p1:p.Gln154Arg
NC_000013.10:g.32900273A>G
NM_000059.3:c.461A>G

Protein change:

Q154R

Links:

dbSNP: rs756335278

NCBI 1000 Genomes Browser:

rs756335278

Molecular consequence:

NM_000059.4:c.461A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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TAB2 TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [Homo sapiens]
TAB2 TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [Homo sapiens]
Gene ID:23118

Gene
Gene Links for GEO Profiles (Select 132482009) (1)
Gene
Homo sapiens isolate CHM13 chromosome 6, alternate assembly T2T-CHM13v2.0
Homo sapiens isolate CHM13 chromosome 6, alternate assembly T2T-CHM13v2.0
gi|2194974009|gnl|ASM:GCF_009914825 f|NC_060930.1||gpp|GPC_000012745.1||gnl|NCBI_GENOMES|119566

Nucleotide
Related gene-specific medical variations for Gene (Select 23118) (161)
ClinVar
BioAssays, RNAi Target, Tested for Gene (Select 23118) (19)
PubChem BioAssay

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002293742	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27257965, 30702160, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002293742

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 29, 2022)

germline

clinical testing

PubMed (3)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients.

Zhong X, Dong Z, Dong H, Li J, Peng Z, Deng L, Zhu X, Sun Y, Lu X, Shen F, Su X, Zhang L, Gu Y, Zheng H.

PLoS One. 2016;11(6):e0156789. doi: 10.1371/journal.pone.0156789.

PubMed [citation]

PMID:: 27257965
PMCID:: PMC4892623

Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.

Bhaskaran SP, Chandratre K, Gupta H, Zhang L, Wang X, Cui J, Kim YC, Sinha S, Jiang L, Lu B, Wu X, Qin Z, Huang T, Wang SM.

Int J Cancer. 2019 Aug 15;145(4):962-973. doi: 10.1002/ijc.32176. Epub 2019 Feb 13.

PubMed [citation]

PMID:: 30702160
PMCID:: PMC6617753

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002293742.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 224453). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 27257965, 30702160). This variant is present in population databases (rs756335278, gnomAD 0.003%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 154 of the BRCA2 protein (p.Gln154Arg).

#	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: Sep 29, 2024

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