NM_000059.4(BRCA2):c.4135del (p.Gln1379fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 20, 2020
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:: RCV000759614.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.4135del (p.Gln1379fs)]

NM_000059.4(BRCA2):c.4135del (p.Gln1379fs)

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.4135del (p.Gln1379fs)

HGVS:

NC_000013.11:g.32338490del
NG_012772.3:g.28011del
NM_000059.4:c.4135delMANE SELECT
NM_000059.4:c.4135delC
NP_000050.3:p.Gln1379fs
LRG_293:g.28011del
NC_000013.10:g.32912627del
NC_000013.10:g.32912627delC
NM_000059.3:c.4135delC
p.(Gln1379ArgfsTer9)

Links:

dbSNP: rs1555283588

NCBI 1000 Genomes Browser:

rs1555283588

Molecular consequence:

NM_000059.4:c.4135del - 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
SCV000889043	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jul 11, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001472778	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Jul 20, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000889043

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jul 11, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001472778

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Pathogenic
(Jul 20, 2020)

germline

clinical testing

Citation Link

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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889043.2

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001472778.1

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

Description

The BRCA2 c.4135delC; p.Gln1379fs variant (rs1555283588) is reported in the literature in an individual at high risk for breast and ovarian cancer (Nelson-Moseke 2013). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, numerous downstream truncating variants have been described in individuals with breast and ovarian cancer and are considered pathogenic (Bhaskaran 2019, Loizidou 2017). Based on available information, the p.Gln1379fs variant is considered to be pathogenic. References: Bhaskaran SP et al. Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. Int J Cancer. 2019 Aug 15;145(4):962-973. Loizidou MA et al. BRCA1 and BRCA2 mutation testing in Cyprus; a population based study. Clin Genet. 2017 Apr;91(4):611-615. Nelson-Moseke AC et al. An unusual BRCA mutation distribution in a high risk cancer genetics clinic. Fam Cancer. 2013;12(1):83-87.

#	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 26, 2024

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