NM_000059.3(BRCA2):c.517G>T (p.Gly173Cys) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Uncertain significance (Last evaluated: Aug 31, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001301980.1

Allele description [Variation Report for NM_000059.3(BRCA2):c.517G>T (p.Gly173Cys)]

NM_000059.3(BRCA2):c.517G>T (p.Gly173Cys)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.517G>T (p.Gly173Cys)
HGVS:
  • NC_000013.11:g.32326499G>T
  • NG_012772.3:g.16020G>T
  • NM_000059.3:c.517G>T
  • NP_000050.2:p.Gly173Cys
  • LRG_293t1:c.517G>T
  • LRG_293:g.16020G>T
  • LRG_293p1:p.Gly173Cys
  • NC_000013.10:g.32900636G>T
  • NM_000059.4:c.517G>TMANE SELECT
Nucleotide change:
745G>T
Protein change:
G173C
Links:
dbSNP: rs397507768
NCBI 1000 Genomes Browser:
rs397507768
Molecular consequence:
  • NM_000059.3:c.517G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001491167Invitaecriteria provided, single submitter
Uncertain significance
(Aug 31, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Multiple sequence variants of BRCA2 exon 7 alter splicing regulation.

Gaildrat P, Krieger S, Di Giacomo D, Abdat J, Révillion F, Caputo S, Vaur D, Jamard E, Bohers E, Ledemeney D, Peyrat JP, Houdayer C, Rouleau E, Lidereau R, Frébourg T, Hardouin A, Tosi M, Martins A.

J Med Genet. 2012 Oct;49(10):609-17. doi: 10.1136/jmedgenet-2012-100965. Epub 2012 Sep 7.

PubMed [citation]
PMID:
22962691

Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice.

Solano AR, Cardoso FC, Romano V, Perazzo F, Bas C, Recondo G, Santillan FB, Gonzalez E, Abalo E, Viniegra M, Michel JD, Nuñez LM, Noblia CM, Mc Lean I, Canton ED, Chacon RD, Cortese G, Varela EB, Greco M, Barrientos ML, Avila SA, Vuotto HD, et al.

Oncotarget. 2017 Sep 1;8(36):60487-60495. doi: 10.18632/oncotarget.10814.

PubMed [citation]
PMID:
28947987
PMCID:
PMC5601155
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001491167.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces glycine with cysteine at codon 173 of the BRCA2 protein (p.Gly173Cys). The glycine residue is weakly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with breast cancer (PMID: 22962691, 28947987, 25777348). ClinVar contains an entry for this variant (Variation ID: 51805). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 30883759). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

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