NM_000059.4(BRCA2):c.7251_7252del (p.His2417fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 27, 2023
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:: RCV000519211.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.7251_7252del (p.His2417fs)]

NM_000059.4(BRCA2):c.7251_7252del (p.His2417fs)

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.7251_7252del (p.His2417fs)

HGVS:

NC_000013.11:g.32355102CA[1]
NG_012772.3:g.44623CA[1]
NM_000059.4:c.7251_7252delMANE SELECT
NP_000050.3:p.His2417fs
LRG_293:g.44623CA[1]
NC_000013.10:g.32929239CA[1]
NC_000013.10:g.32929239_32929240del
NM_000059.3:c.7251_7252delCA
NM_000059.4:c.7251_7252del
p.H2417QFS*3

Nucleotide change:

7479delCA

Protein change:

H2417fs

Links:

dbSNP: rs397507907

NCBI 1000 Genomes Browser:

rs397507907

Molecular consequence:

NM_000059.4:c.7251_7252del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000617471	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 27, 2023)	germline	clinical testing	Citation Link,
SCV000887909	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jan 20, 2023)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 29446198, 29753700, 15131399, 24784157, 26843898, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000617471

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 27, 2023)

germline

clinical testing

Citation Link,

SCV000887909

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jan 20, 2023)

unknown

clinical testing

PubMed (6)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH, Thomassen M, Weitzel JN, Chan TL, Couch FJ, Goldgar DE, Kruse TA, Palmero EI, Park SK, Torres D, van Rensburg EJ, McGuffog L, Parsons MT, et al.

Hum Mutat. 2018 May;39(5):593-620. doi: 10.1002/humu.23406. Epub 2018 Mar 12.

PubMed [citation]

PMID:: 29446198
PMCID:: PMC5903938

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

Waszak SM, Northcott PA, Buchhalter I, Robinson GW, Sutter C, Groebner S, Grund KB, Brugières L, Jones DTW, Pajtler KW, Morrissy AS, Kool M, Sturm D, Chavez L, Ernst A, Brabetz S, Hain M, Zichner T, Segura-Wang M, Weischenfeldt J, Rausch T, Mardin BR, et al.

Lancet Oncol. 2018 Jun;19(6):785-798. doi: 10.1016/S1470-2045(18)30242-0. Epub 2018 May 9.

PubMed [citation]

PMID:: 29753700
PMCID:: PMC5984248

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000617471.3

#	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; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Lubinski 2004, Cybulski 2014, Kluska 2015); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as BRCA2 7479_7480del, 7479delCA, 7249delCA, and 7249_7250delCA; This variant is associated with the following publications: (PMID: 15131399, 27225819, 24784157, 26843898, 25330149, 25948282, 29753700, 30787465)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000887909.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This frameshift variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with hereditary breast and/or ovarian cancer (PMID: 26843898 (2016)) as well as other cancers (PMID: 15131399 (2004), 29753700 (2018)). Based on the available information, this variant is classified as pathogenic.

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

Last Updated: Nov 3, 2024

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