NM_000059.4(BRCA2):c.2774_2775del (p.Ser925fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 3, 2020
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:: RCV001260340.9

Allele description [Variation Report for NM_000059.4(BRCA2):c.2774_2775del (p.Ser925fs)]

NM_000059.4(BRCA2):c.2774_2775del (p.Ser925fs)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.2774_2775del (p.Ser925fs)

HGVS:

NC_000013.11:g.32337127CT[1]
NG_012772.3:g.26648CT[1]
NM_000059.4:c.2774_2775delMANE SELECT
NP_000050.3:p.Ser925fs
LRG_293:g.26648CT[1]
NC_000013.10:g.32911264CT[1]
NM_000059.3:c.2774_2775delCT
p.(Ser925TyrfsTer10)

Protein change:

S925fs

Links:

dbSNP: rs397507641

NCBI 1000 Genomes Browser:

rs397507641

Molecular consequence:

NM_000059.4:c.2774_2775del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

Recent activity

Clear Turn Off Turn On

RAB21, member RAS oncogene family [Mus musculus]
RAB21, member RAS oncogene family [Mus musculus]
gi|32822759|gb|AAH55042.1|

Protein
Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/USA/DC-...
Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/USA/DC-CDC-LC0066950/2021, complete genome
gi|2050754383|gb|MZ372090.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001437272	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 3, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27974384, 19715467 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001437272

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Sep 3, 2020)

germline

clinical testing

PubMed (2)
[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

BRCA Testing by Single-Molecule Molecular Inversion Probes.

Neveling K, Mensenkamp AR, Derks R, Kwint M, Ouchene H, Steehouwer M, van Lier B, Bosgoed E, Rikken A, Tychon M, Zafeiropoulou D, Castelein S, Hehir-Kwa J, Tjwan Thung D, Hofste T, Lelieveld SH, Bertens SM, Adan IB, Eijkelenboom A, Tops BB, Yntema H, Stokowy T, et al.

Clin Chem. 2017 Feb;63(2):503-512. doi: 10.1373/clinchem.2016.263897. Epub 2016 Dec 14.

PubMed [citation]

PMID:: 27974384

Identification of a novel pathogenic mutation in BRCA2 in a Spanish breast-ovarian cancer family.

Torres A, Gumà J, Rodríguez M, Brunet J, Borràs J.

Genet Test Mol Biomarkers. 2009 Oct;13(5):631-4. doi: 10.1089/gtmb.2009.0040.

PubMed [citation]

PMID:: 19715467

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001437272.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: BRCA2 c.2774_2775delCT (p.Ser925TyrfsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250816 control chromosomes. c.2774_2775delCT has been reported in the literature in a family affected with Hereditary Breast And Ovarian Cancer Syndrome (Torres_2009). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. An expert panel (ENIGMA) has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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: Nov 3, 2024

ClinVar

Relating variation to medicine