NM_000059.4(BRCA2):c.658_659del (p.Val220fs) AND BRCA2-Related Disorders

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
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:: RCV003335024.1

Allele description

NM_000059.4(BRCA2):c.658_659del (p.Val220fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.658_659del (p.Val220fs)

Other names:

886_887delGT

HGVS:

NC_000013.10:g.32903605_32903606del
NC_000013.11:g.32329469_32329470del
NG_012772.3:g.18990_18991del
NM_000059.4:c.658_659delMANE SELECT
NP_000050.3:p.Val220fs
LRG_293:g.18990_18991del
NC_000013.10:g.32903605_32903606del
NC_000013.10:g.32903606_32903607del
NC_000013.10:g.32903606_32903607del
NC_000013.10:g.32903606_32903607delGT
NC_000013.11:g.32329469_32329470delGT
NM_000059.3:c.657_658del
NM_000059.3:c.658_659delGT
U43746.1:n.886_887delGT
p.V220IFS*4
p.V220IfsX4
p.Val220Ilefs*4
p.Val220IlefsX4
p.Val220fs

Nucleotide change:

886delGT

Links:

Breast Cancer Information Core (BIC) (BRCA2): 886&base_change=del GT; OMIM: 600185.0027; dbSNP: rs80359604

NCBI 1000 Genomes Browser:

rs80359604

Molecular consequence:

NM_000059.4:c.658_659del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: BRCA2-Related Disorders
Identifiers:: MedGen: CN239275

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046239	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004046239

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046239.1

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

Description

This frameshifting variant in exon 8 of 28 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported in individuals with breast and ovarian cancer (PMID: 22923021, 23767878, 28324225). This variant has also been reported as a compound heterozygous change in patients with Fanconi anemia (PMID: 16825431). Loss-of-function variation in BRCA2 is an established mechanism of disease (PMID: 20104584). The c.658_659del (p.Val220IlefsTer4) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.005% (13/276414) and thus is presumed to be rare. Based on the available evidence, the c.658_659del (p.Val220IlefsTer4) variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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