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NM_000059.4(BRCA2):c.5655C>A (p.Cys1885Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 15, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000220539.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.5655C>A (p.Cys1885Ter)]

NM_000059.4(BRCA2):c.5655C>A (p.Cys1885Ter)

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.5655C>A (p.Cys1885Ter)
Other names:
p.C1885*:TGC>TGA
HGVS:
  • NC_000013.11:g.32340010C>A
  • NG_012772.3:g.29531C>A
  • NM_000059.4:c.5655C>AMANE SELECT
  • NP_000050.2:p.Cys1885Ter
  • NP_000050.3:p.Cys1885Ter
  • LRG_293t1:c.5655C>A
  • LRG_293:g.29531C>A
  • LRG_293p1:p.Cys1885Ter
  • NC_000013.10:g.32914147C>A
  • NM_000059.3:c.5655C>A
  • U43746.1:n.5883C>A
  • p.Cys1885*
Protein change:
C1885*
Links:
dbSNP: rs80358789
NCBI 1000 Genomes Browser:
rs80358789
Molecular consequence:
  • NM_000059.4:c.5655C>A - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000278194Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Jun 9, 2021) 		germlineclinical testing

Citation Link,

SCV000905016Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Nov 15, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]
PMID:
25186627

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH, Thomassen M, Weitzel JN, Chan TL, Couch FJ, Goldgar DE, Kruse TA, Palmero EI, Park SK, Torres D, van Rensburg EJ, McGuffog L, Parsons MT, et al.

Hum Mutat. 2018 May;39(5):593-620. doi: 10.1002/humu.23406. Epub 2018 Mar 12.

PubMed [citation]
PMID:
29446198
PMCID:
PMC5903938
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000278194.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The p.C1885* pathogenic mutation (also known as c.5655C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 5655. This changes the amino acid from a cysteine to a stop codon within coding exon 10. This mutation has been identified in a female patient with breast cancer (Tung N et al. Cancer. 2015 Jan 1;121(1):25-33). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV000905016.4

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

Description

This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least one individual affected with breast cancer (PMID: 25186627) and has been identified in 3 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: Apr 20, 2024