NM_000059.4(BRCA2):c.2658_2659del (p.Asn886fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 14, 2019
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:: RCV000482987.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.2658_2659del (p.Asn886fs)]

NM_000059.4(BRCA2):c.2658_2659del (p.Asn886fs)

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.2658_2659del (p.Asn886fs)

HGVS:

NC_000013.11:g.32337013_32337014del
NG_012772.3:g.26534_26535del
NM_000059.4:c.2658_2659delMANE SELECT
NP_000050.2:p.Asn886fs
NP_000050.3:p.Asn886fs
LRG_293t1:c.2658_2659del
LRG_293:g.26534_26535del
LRG_293p1:p.Asn886fs
NC_000013.10:g.32911150_32911151del
NM_000059.3:c.2658_2659del
NM_000059.3:c.2658_2659delTG

Nucleotide change:

2886delTG

Protein change:

N886fs

Links:

dbSNP: rs397507291

NCBI 1000 Genomes Browser:

rs397507291

Molecular consequence:

NM_000059.4:c.2658_2659del - 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
SCV000569842	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Mar 31, 2016)	germline	clinical testing	Citation Link,
SCV001133720	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Feb 14, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000569842

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Mar 31, 2016)

germline

clinical testing

Citation Link,

SCV001133720

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Feb 14, 2019)

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	germline	yes	not provided	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

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 GeneDx, SCV000569842.3

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

Description

This deletion of 2 nucleotides in BRCA2 is denoted c.2658_2659delTG at the cDNA level and p.Asn886LysfsX3 (N886KfsX3) at the protein level. The normal sequence, with the bases that are deleted in braces, is ACAA[TG]AGAA. The deletion causes a frameshift which changes an Asparagine to a Lysine at codon 886, and creates a premature stop codon at position 3 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.

#	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, SCV001133720.2

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

Description

The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.

#	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: Sep 29, 2024

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