NM_000059.4(BRCA2):c.538_539del (p.Ile180fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 10, 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:: RCV000657218.11

Allele description [Variation Report for NM_000059.4(BRCA2):c.538_539del (p.Ile180fs)]

NM_000059.4(BRCA2):c.538_539del (p.Ile180fs)

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.538_539del (p.Ile180fs)

Other names:

766delAT

HGVS:

NC_000013.11:g.32326518AT[1]
NG_012772.3:g.16039AT[1]
NM_000059.4:c.538_539delMANE SELECT
NP_000050.3:p.Ile180fs
LRG_293:g.16039AT[1]
NC_000013.10:g.32900655AT[1]
NC_000013.10:g.32900655_32900656del
NM_000059.3:c.538_539delAT
U43746.1:n.766_767delAT

Protein change:

I180fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 766&base_change=del AT; dbSNP: rs80359510

NCBI 1000 Genomes Browser:

rs80359510

Molecular consequence:

NM_000059.4:c.538_539del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

B3galt5 [Phodopus roborovskii]
B3galt5 [Phodopus roborovskii]
Gene ID:127227558

Gene
Fut1 [Phodopus roborovskii]
Fut1 [Phodopus roborovskii]
Gene ID:127213939

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000778944	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 13, 2016)	germline	clinical testing	Citation Link,
SCV001449536	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 10, 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

SCV000778944

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Dec 13, 2016)

germline

clinical testing

Citation Link,

SCV001449536

Clinical Genetics and Genomics, Karolinska University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 10, 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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000778944.1

#	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 two nucleotides in BRCA2 is denoted c.538_539delAT at the cDNA level and p.Ile180PhefsX2 (I180FfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACAT[delAT]TTCT. The deletion causes a frameshift which changes an Isoleucine to a Phenylalanine at codon 180, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.538_539delAT, also defined as 766_767delAT, has been observed in an individual with a personal history of prostate cancer and family history of breast cancer (de Juan 2015). 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 Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449536.1

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

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine