NM_000059.4(BRCA2):c.7579del (p.Ala2526_Val2527insTer) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 16, 2022
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:: RCV001860076.12

Allele description [Variation Report for NM_000059.4(BRCA2):c.7579del (p.Ala2526_Val2527insTer)]

NM_000059.4(BRCA2):c.7579del (p.Ala2526_Val2527insTer)

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.7579del (p.Ala2526_Val2527insTer)

HGVS:

NC_000013.11:g.32356571del
NG_012772.3:g.46092del
NM_000059.4:c.7579delMANE SELECT
NP_000050.2:p.Ala2526_Val2527insTer
NP_000050.3:p.Ala2526_Val2527insTer
LRG_293t1:c.7579del
LRG_293:g.46092del
LRG_293p1:p.Ala2526_Val2527insTer
NC_000013.10:g.32930708del
NM_000059.3:c.7579del
NM_000059.3:c.7579delG

Links:

dbSNP: rs1555286294

NCBI 1000 Genomes Browser:

rs1555286294

Molecular consequence:

NM_000059.4:c.7579del - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002247041	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 16, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 30014164, 30207912, 31558676, 20104584, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002247041

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 16, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

The yield of full BRCA1/2 genotyping in Israeli high-risk breast/ovarian cancer patients who do not carry the predominant mutations.

Barnes-Kedar I, Bernstein-Molho R, Ginzach N, Hartmajer S, Shapira T, Magal N, Kalis ML, Peretz T, Shohat M, Basel-Salmon L, Friedman E, Bazak L, Goldberg Y.

Breast Cancer Res Treat. 2018 Nov;172(1):151-157. doi: 10.1007/s10549-018-4887-7. Epub 2018 Jul 16.

PubMed [citation]

PMID:: 30014164

Essential Role of BRCA2 in Ovarian Development and Function.

Weinberg-Shukron A, Rachmiel M, Renbaum P, Gulsuner S, Walsh T, Lobel O, Dreifuss A, Ben-Moshe A, Zeligson S, Segel R, Shore T, Kalifa R, Goldberg M, King MC, Gerlitz O, Levy-Lahad E, Zangen D.

N Engl J Med. 2018 Sep 13;379(11):1042-1049. doi: 10.1056/NEJMoa1800024.

PubMed [citation]

PMID:: 30207912
PMCID:: PMC6230262

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002247041.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 491326). This premature translational stop signal has been observed in individual(s) with breast cancer and/or clinical features of Fanconi anemia (PMID: 30014164, 30207912, 31558676). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val2527*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584).

#	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: Oct 20, 2024

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