NM_000059.4(BRCA2):c.2488_2489insG (p.Asn830fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 2, 2018
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:: RCV004018382.2

Allele description [Variation Report for NM_000059.4(BRCA2):c.2488_2489insG (p.Asn830fs)]

NM_000059.4(BRCA2):c.2488_2489insG (p.Asn830fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.2488_2489insG (p.Asn830fs)

HGVS:

NC_000013.11:g.32336843_32336844insG
NG_012772.3:g.26364_26365insG
NM_000059.4:c.2488_2489insGMANE SELECT
NM_001406719.1:c.2488_2489insG
NM_001406720.1:c.2488_2489insG
NM_001406721.1:c.1909+3456_1909+3457insG
NM_001406722.1:c.424+5813_424+5814insG
NP_000050.2:p.Asn830Argfs
NP_000050.3:p.Asn830fs
NP_001393648.1:p.Asn830fs
NP_001393649.1:p.Asn830fs
LRG_293t1:c.2488_2489insG
LRG_293:g.26364_26365insG
LRG_293p1:p.Asn830Argfs
NC_000013.10:g.32910980_32910981insG
NM_000059.3:c.2488_2489insG
NR_176251.1:n.2687_2688insG

Protein change:

N830fs

Molecular consequence:

NM_000059.4:c.2488_2489insG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406719.1:c.2488_2489insG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406720.1:c.2488_2489insG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406721.1:c.1909+3456_1909+3457insG - intron variant - [Sequence Ontology: SO:0001627]
NM_001406722.1:c.424+5813_424+5814insG - intron variant - [Sequence Ontology: SO:0001627]
NR_176251.1:n.2687_2688insG - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848196	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 2, 2018)	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

SCV004848196

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 2, 2018)

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	unknown	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848196.1

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

Description

The p.Asn830fs variant in BRCA2 has not been previously reported in individuals with BRCA2-associated cancer and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 830 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in hereditary breast and ovarian cancer syndrome (HBOC). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon absence from controls and its predicted impact on the protein. ACMG/AMP Criteria applied: PVS1; PM2.

#	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: Sep 1, 2024

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