NM_000059.4(BRCA2):c.771_775del (p.Asn257fs) AND Familial cancer of breast

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 24, 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:: RCV000056288.21

Allele description [Variation Report for NM_000059.4(BRCA2):c.771_775del (p.Asn257fs)]

NM_000059.4(BRCA2):c.771_775del (p.Asn257fs)

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.771_775del (p.Asn257fs)

Other names:

995del5

HGVS:

NC_000013.10:g.32905141_32905145del
NC_000013.11:g.32331008_32331012del
NG_012772.3:g.20529_20533del
NM_000059.4:c.771_775delMANE SELECT
NP_000050.3:p.Asn257fs
LRG_293:g.20529_20533del
NC_000013.10:g.32905141_32905145del
NC_000013.10:g.32905145_32905149del
NC_000013.10:g.32905145_32905149del
NC_000013.10:g.32905145_32905149delTCAAA
NM_000059.3:c.771_775delTCAAA
NM_000059.4:c.771_775delTCAAA
U43746.1:n.995_999delCAAAT
U43746.1:n.999_1003delTCAAA
p.Asn257Lysfs*17
p.N257KFS*17
p.N257KfsX17

Nucleotide change:

999del5

Links:

Breast Cancer Information Core (BIC) (BRCA2): 995&base_change=del CAAAT; Breast Cancer Information Core (BIC) (BRCA2): 999&base_change=del TCAAA; OMIM: 600185.0010; dbSNP: rs80359671

NCBI 1000 Genomes Browser:

rs80359671

Molecular consequence:

NM_000059.4:c.771_775del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

Recent activity

Clear Turn Off Turn On

Mus musculus cDNA clone IMAGE:5353354, containing frame-shift errors
Mus musculus cDNA clone IMAGE:5353354, containing frame-shift errors
gi|23958384|gb|BC023740.1|

Nucleotide
Mus musculus zinc metallopeptidase, STE24 homolog (S. cerevisiae), mRNA (cDNA cl...
Mus musculus zinc metallopeptidase, STE24 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:5356334)
gi|23337013|gb|BC037610.1|

Nucleotide
BUD13 homolog [Mus musculus]
BUD13 homolog [Mus musculus]
gi|22122459|ref|NP_666112.1|

Protein
Bibliography - Diagnosis and Management of Dental Caries
Bibliography - Diagnosis and Management of Dental Caries

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
SCV000693552	GeneKor MSA	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 1, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004213709	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 24, 2023)	unknown	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

SCV000693552

GeneKor MSA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 1, 2020)

germline

clinical testing

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

SCV004213709

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 24, 2023)

unknown

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	unknown	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

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 GeneKor MSA, SCV000693552.3

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

Description

This is a deletion of five base pairs, which results in frameshift and creation of a novel stop codon 17 amino acid residues later. The result is a truncated, non-functional protein. Truncating variants in BRCA2 are known to be pathogenic.This variant is also known as 999del5 in the literature and is a common cause of breast and ovarian cancer in the Icelandic population but has been reported also in individuals of other ethnicities (PMID: 9150155, 8673089, 8589730 ; 25863477 ).The mutation database Clinvar contains entries for this variant (Variation ID:9326).

#	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 Baylor Genetics, SCV004213709.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

ClinVar

Relating variation to medicine