NM_000059.3(BRCA2):c.442T>C (p.Cys148Arg) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Uncertain significance (Last evaluated: Sep 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000044413.9

Allele description [Variation Report for NM_000059.3(BRCA2):c.442T>C (p.Cys148Arg)]

NM_000059.3(BRCA2):c.442T>C (p.Cys148Arg)

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.442T>C (p.Cys148Arg)
HGVS:
  • NC_000013.11:g.32326117T>C
  • NG_012772.3:g.15638T>C
  • NM_000059.3:c.442T>C
  • NP_000050.2:p.Cys148Arg
  • LRG_293t1:c.442T>C
  • LRG_293:g.15638T>C
  • LRG_293p1:p.Cys148Arg
  • NC_000013.10:g.32900254T>C
  • NM_000059.4:c.442T>CMANE SELECT
  • U43746.1:n.670T>C
Nucleotide change:
670T>C
Protein change:
C148R
Links:
dbSNP: rs80358677
NCBI 1000 Genomes Browser:
rs80358677
Molecular consequence:
  • NM_000059.3:c.442T>C - 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
SCV000072426Invitaecriteria provided, single submitter
Uncertain significance
(Sep 11, 2020)
germlineclinical testing

PubMed (3)
[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

LOVD v.2.0: the next generation in gene variant databases.

Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT.

Hum Mutat. 2011 May;32(5):557-63. doi: 10.1002/humu.21438. Epub 2011 Feb 22.

PubMed [citation]
PMID:
21520333

The breast cancer information core: database design, structure, and scope.

Szabo C, Masiello A, Ryan JF, Brody LC.

Hum Mutat. 2000;16(2):123-31.

PubMed [citation]
PMID:
10923033
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000072426.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces cysteine with arginine at codon 148 of the BRCA2 protein (p.Cys148Arg). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs80358677, ExAC 0.009%). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333) and Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 51647). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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 23, 2021

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