NM_000059.4(BRCA2):c.1773_1776del (p.Ile591fs) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Feb 6, 2024
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:: RCV000160268.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.1773_1776del (p.Ile591fs)]

NM_000059.4(BRCA2):c.1773_1776del (p.Ile591fs)

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.1773_1776del (p.Ile591fs)

Other names:

2001del4; 2000del4; 2000_2003delTTTA

HGVS:

NC_000013.10:g.32907383_32907386del
NC_000013.11:g.32333247TTAT[1]
NG_012772.3:g.22768TTAT[1]
NM_000059.4:c.1773_1776delMANE SELECT
NP_000050.3:p.Ile591fs
LRG_293:g.22768TTAT[1]
NC_000013.10:g.32907383_32907386del
NC_000013.10:g.32907384TTAT[1]
NC_000013.10:g.32907388_32907391del
NC_000013.10:g.32907388_32907391delTTAT
NM_000059.3:c.1773_1776delTTAT
NM_000059.4:c.1773_1776delTTAT
U43746.1:n.2000_2003delTTTA
U43746.1:n.2001_2004delTTAT
p.I591MfsX22
p.Ile591Metfs*22
U43746.1:n.2001_2004delTATT

Protein change:

I591fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 2000&base_change=del TTTA; Breast Cancer Information Core (BIC) (BRCA2): 2001&base_change=del TATT; Breast Cancer Information Core (BIC) (BRCA2): 2001&base_change=del TTAT; dbSNP: rs80359304

NCBI 1000 Genomes Browser:

rs80359304

Molecular consequence:

NM_000059.4:c.1773_1776del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000210715	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 15, 2022)	germline	clinical testing	Citation Link,
SCV001450407	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 22, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001550959	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Uncertain significance	unknown	clinical testing
SCV004242827	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 6, 2024)	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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
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 GeneDx, SCV000210715.6

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Kanaan et al., 2003; Thirthagiri et al., 2008; Novakovic et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 2001_2004del; This variant is associated with the following publications: (PMID: 18393245, 28993434, 32846166, 30787465, 31825140, 32719484, 26295337, 20104584, 12942367, 28439188, 28888541, 29446198, Bahsi2020[case report], 30702160, 24123850, 30875412, 18627636, 22923021)

#	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

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001450407.1

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

#	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		2	not provided	not provided	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001550959.1

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

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

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV004242827.1

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

#	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

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