NM_032043.2(BRIP1):c.1652C>A (p.Ala551Glu) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 4, 2017
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:: RCV000205457.3

Allele description

NM_032043.2(BRIP1):c.1652C>A (p.Ala551Glu)

Gene:

BRIP1:BRCA1 interacting protein C-terminal helicase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.2(BRIP1):c.1652C>A (p.Ala551Glu)

HGVS:

NC_000017.11:g.61780982G>T
NG_007409.2:g.87578C>A
NM_032043.2:c.1652C>A
NP_114432.2:p.Ala551Glu
LRG_300t1:c.1652C>A
LRG_300:g.87578C>A
LRG_300p1:p.Ala551Glu
NC_000017.10:g.59858343G>T

Protein change:

A551E

Links:

dbSNP: rs375246789

NCBI 1000 Genomes Browser:

rs375246789

Molecular consequence:

NM_032043.2:c.1652C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: CHEK2-Related Breast Cancer
Identifiers:: MedGen: C0346153; OMIM: 114480

Name:: Fanconi anemia, complementation group J (FANCJ)
Identifiers:: MedGen: C1836860; Orphanet: 84; OMIM: 609054

Recent activity

Clear Turn Off Turn On

pulmonary surfactant-associated protein [Homo sapiens]
pulmonary surfactant-associated protein [Homo sapiens]
gi|190670|gb|AAA60211.1|

Protein
Pericrocotus ethologus strain:NA
Pericrocotus ethologus strain:NA
Pericrocotus ethologus

BioProject
SBNO2 strawberry notch homolog 2 [Sus scrofa]
SBNO2 strawberry notch homolog 2 [Sus scrofa]
Gene ID:100623993

Gene
DDX56 DEAD-box helicase 56 [Sus scrofa]
DDX56 DEAD-box helicase 56 [Sus scrofa]
Gene ID:100513388

Gene
DDX51 DEAD-box helicase 51 [Sus scrofa]
DDX51 DEAD-box helicase 51 [Sus scrofa]
Gene ID:100512865

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
SCV000259470	Invitae	criteria provided, single submitter (Nykamp K et al. (Genet Med 2017))	Uncertain significance (Dec 4, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25452441, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000259470

Invitae

criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))

Uncertain significance
(Dec 4, 2017)

germline

clinical testing

PubMed (2)
[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

Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer.

Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, Olson JE, Godwin AK, Pankratz VS, Olswold C, Slettedahl S, Hallberg E, Guidugli L, Davila JI, Beckmann MW, Janni W, Rack B, Ekici AB, Slamon DJ, Konstantopoulou I, Fostira F, Vratimos A, et al.

J Clin Oncol. 2015 Feb 1;33(4):304-11. doi: 10.1200/JCO.2014.57.1414. Epub 2014 Dec 1.

PubMed [citation]

PMID:: 25452441
PMCID:: PMC4302212

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000259470.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces alanine with glutamic acid at codon 551 of the BRIP1 protein (p.Ala551Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with triple-negative breast cancer (PMID: 25452441). ClinVar contains an entry for this variant (Variation ID: 219544). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

#	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 13, 2018

ClinVar

Relating variation to medicine