NM_000059.4(BRCA2):c.4000_4001del (p.Leu1334fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 26, 2021
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:: RCV000637469.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.4000_4001del (p.Leu1334fs)]

NM_000059.4(BRCA2):c.4000_4001del (p.Leu1334fs)

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.4000_4001del (p.Leu1334fs)

HGVS:

NC_000013.11:g.32338355_32338356del
NG_012772.3:g.27876_27877del
NM_000059.4:c.4000_4001delMANE SELECT
NP_000050.2:p.Leu1334fs
NP_000050.3:p.Leu1334fs
LRG_293t1:c.4000_4001del
LRG_293:g.27876_27877del
LRG_293p1:p.Leu1334fs
NC_000013.10:g.32912492_32912493del
NM_000059.3:c.4000_4001del
NM_000059.3:c.4000_4001delTT
p.L1334RfsX3

Nucleotide change:

4228delTT

Protein change:

L1334fs

Links:

dbSNP: rs398122775

NCBI 1000 Genomes Browser:

rs398122775

Molecular consequence:

NM_000059.4:c.4000_4001del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Homo sapiens mRNA for KIAA0298 protein, partial cds
Homo sapiens mRNA for KIAA0298 protein, partial cds
gi|6634008|dbj|AB002296.2|

Nucleotide
ISYNA1 [Apteryx rowi]
ISYNA1 [Apteryx rowi]
Gene ID:112967723

Gene
URA10 orotate phosphoribosyltransferase URA10 [Saccharomyces cerevisiae S288C]
URA10 orotate phosphoribosyltransferase URA10 [Saccharomyces cerevisiae S288C]
Gene ID:855313

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000758929	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 26, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26681312, 20104584, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000758929

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 26, 2021)

germline

clinical testing

PubMed (3)
[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

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2. doi: 10.1038/gim.2016.21.

PubMed [citation]

PMID:: 26681312
PMCID:: PMC4985612

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A, Haile RW, Malone KE, Capanu M, Diep A, Törngren T, Teraoka S, Begg CB, Thomas DC, Concannon P, Mellemkjaer L, Bernstein L, Tellhed L, Xue S, Olson ER, Liang X, Dolle J, Børresen-Dale AL, Bernstein JL.

Hum Mutat. 2010 Mar;31(3):E1200-40. doi: 10.1002/humu.21202.

PubMed [citation]

PMID:: 20104584
PMCID:: PMC2928257

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000758929.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 91812). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26681312). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu1334Argfs*3) 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: Nov 10, 2024

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