NM_000059.4(BRCA2):c.5909C>G (p.Ser1970Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 13, 2017
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:: RCV000573759.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.5909C>G (p.Ser1970Ter)]

NM_000059.4(BRCA2):c.5909C>G (p.Ser1970Ter)

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.5909C>G (p.Ser1970Ter)

HGVS:

NC_000013.11:g.32340264C>G
NG_012772.3:g.29785C>G
NM_000059.4:c.5909C>GMANE SELECT
NP_000050.2:p.Ser1970Ter
NP_000050.3:p.Ser1970Ter
LRG_293t1:c.5909C>G
LRG_293:g.29785C>G
LRG_293p1:p.Ser1970Ter
NC_000013.10:g.32914401C>G
NM_000059.3:c.5909C>G

Protein change:

S1970*

Links:

dbSNP: rs80358824

NCBI 1000 Genomes Browser:

rs80358824

Molecular consequence:

NM_000059.4:c.5909C>G - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000664816	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 13, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20736950, 24556621, 27153395, 8988179 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000664816

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 13, 2017)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis.

Edwards SM, Evans DG, Hope Q, Norman AR, Barbachano Y, Bullock S, Kote-Jarai Z, Meitz J, Falconer A, Osin P, Fisher C, Guy M, Jhavar SG, Hall AL, O'Brien LT, Gehr-Swain BN, Wilkinson RA, Forrest MS, Dearnaley DP, Ardern-Jones AT, Page EC, Easton DF, et al.

Br J Cancer. 2010 Sep 7;103(6):918-24. doi: 10.1038/sj.bjc.6605822. Epub 2010 Aug 24.

PubMed [citation]

PMID:: 20736950
PMCID:: PMC2948551

Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease.

Leongamornlert D, Saunders E, Dadaev T, Tymrakiewicz M, Goh C, Jugurnauth-Little S, Kozarewa I, Fenwick K, Assiotis I, Barrowdale D, Govindasami K, Guy M, Sawyer E, Wilkinson R; UKGPCS Collaborators., Antoniou AC, Eeles R, Kote-Jarai Z.

Br J Cancer. 2014 Mar 18;110(6):1663-72. doi: 10.1038/bjc.2014.30. Epub 2014 Feb 20.

PubMed [citation]

PMID:: 24556621
PMCID:: PMC3960610

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000664816.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.S1970* pathogenic mutation (also known as c.5909C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 5909. This changes the amino acid from a serine to a stop codon within coding exon 10. This mutation has been identified in multiple individuals with hereditary breast and ovarian cancer (HBOC) syndrome-associated cancers, including ovarian, prostate, and breast cancers (Gayther SA et al. Nat. Genet. 1997 Jan;15:103-5; Edwards SM et al. Br. J. Cancer. 2010 Sep;103:918-24; Leongamornlert D et al. Br. J. Cancer. 2014 Mar;110:1663-72; Maxwell KN et al. Am. J. Hum. Genet. 2016 May;98:801-17). 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.

#	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: May 1, 2024

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