NM_000059.4(BRCA2):c.483T>G (p.Cys161Trp) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 9, 2021
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:: RCV001852941.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.483T>G (p.Cys161Trp)]

NM_000059.4(BRCA2):c.483T>G (p.Cys161Trp)

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.483T>G (p.Cys161Trp)

HGVS:

NC_000013.11:g.32326249T>G
NG_012772.3:g.15770T>G
NM_000059.4:c.483T>GMANE SELECT
NP_000050.2:p.Cys161Trp
NP_000050.3:p.Cys161Trp
LRG_293t1:c.483T>G
LRG_293:g.15770T>G
LRG_293p1:p.Cys161Trp
NC_000013.10:g.32900386T>G
NM_000059.3:c.483T>G

Protein change:

C161W

Links:

dbSNP: rs397507745

NCBI 1000 Genomes Browser:

rs397507745

Molecular consequence:

NM_000059.4:c.483T>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

Recent activity

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spastin, partial [Rhagoletis zephyria]
spastin, partial [Rhagoletis zephyria]
gi|2049814810|gb|QWJ75126.1|

Protein
NADH dehydrogenase subunit 5 (mitochondrion) [Rhagoletis zephyria]
NADH dehydrogenase subunit 5 (mitochondrion) [Rhagoletis zephyria]
gi|2044005675|gb|QVT11292.1|

Protein
Mus musculus cysteine-serine-rich nuclear protein 2, mRNA (cDNA clone MGC:28165 ...
Mus musculus cysteine-serine-rich nuclear protein 2, mRNA (cDNA clone MGC:28165 IMAGE:3985077), complete cds
gi|23273389|gb|BC035295.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002132223	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 9, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29263802, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002132223

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 9, 2021)

germline

clinical testing

PubMed (2)
[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

Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore.

Wong ESY, Shekar S, Met-Domestici M, Chan C, Sze M, Yap YS, Rozen SG, Tan MH, Ang P, Ngeow J, Lee ASG.

NPJ Genom Med. 2016;1:15003. doi: 10.1038/npjgenmed.2015.3.

PubMed [citation]

PMID:: 29263802
PMCID:: PMC5685290

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002132223.3

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

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. This variant has been observed in individual(s) with breast cancer (PMID: 29263802). ClinVar contains an entry for this variant (Variation ID: 51723). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tryptophan at codon 161 of the BRCA2 protein (p.Cys161Trp). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tryptophan.

#	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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