NM_000059.3(BRCA2):c.4759G>A (p.Ala1587Thr) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Uncertain significance (Last evaluated: Jun 6, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000690936.3

Allele description [Variation Report for NM_000059.3(BRCA2):c.4759G>A (p.Ala1587Thr)]

NM_000059.3(BRCA2):c.4759G>A (p.Ala1587Thr)

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.4759G>A (p.Ala1587Thr)
HGVS:
  • NC_000013.11:g.32339114G>A
  • NG_012772.3:g.28635G>A
  • NM_000059.3:c.4759G>A
  • NP_000050.2:p.Ala1587Thr
  • LRG_293t1:c.4759G>A
  • LRG_293:g.28635G>A
  • LRG_293p1:p.Ala1587Thr
  • NC_000013.10:g.32913251G>A
  • p.A1587T
Protein change:
A1587T
Links:
dbSNP: rs56137239
NCBI 1000 Genomes Browser:
rs56137239
Molecular consequence:
  • NM_000059.3:c.4759G>A - 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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000818667Invitaecriteria provided, single submitter
Uncertain significance
(Jun 6, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer.

Grant RC, Selander I, Connor AA, Selvarajah S, Borgida A, Briollais L, Petersen GM, Lerner-Ellis J, Holter S, Gallinger S.

Gastroenterology. 2015 Mar;148(3):556-64. doi: 10.1053/j.gastro.2014.11.042. Epub 2014 Dec 2.

PubMed [citation]
PMID:
25479140
PMCID:
PMC4339623

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000818667.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces alanine with threonine at codon 1587 of the BRCA2 protein (p.Ala1587Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with pancreatic cancer (PMID: 25479140). ClinVar contains an entry for this variant (Variation ID: 186987). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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: Jun 14, 2021

Support Center