NM_032043.3(BRIP1):c.1262A>T (p.Glu421Val) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 27, 2020
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:: RCV001348981.8

Allele description [Variation Report for NM_032043.3(BRIP1):c.1262A>T (p.Glu421Val)]

NM_032043.3(BRIP1):c.1262A>T (p.Glu421Val)

Gene:

BRIP1:BRCA1 interacting DNA helicase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.3(BRIP1):c.1262A>T (p.Glu421Val)

HGVS:

NC_000017.11:g.61799178T>A
NG_007409.2:g.69382A>T
NM_032043.3:c.1262A>TMANE SELECT
NP_114432.2:p.Glu421Val
LRG_300:g.69382A>T
NC_000017.10:g.59876539T>A

Protein change:

E421V

Links:

dbSNP: rs2077948964

NCBI 1000 Genomes Browser:

rs2077948964

Molecular consequence:

NM_032043.3:c.1262A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Name:: Fanconi anemia complementation group J
Identifiers:: MONDO: MONDO:0012187; MedGen: C1836860; Orphanet: 84; OMIM: 609054

Recent activity

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PREDICTED: Cucurbita moschata EPIDERMAL PATTERNING FACTOR-like protein 2 (LOC111...
PREDICTED: Cucurbita moschata EPIDERMAL PATTERNING FACTOR-like protein 2 (LOC111457464), transcript variant X1, mRNA
gi|1279804214|ref|XM_023099669.1|

Nucleotide
Homo sapiens low density lipoprotein receptor (LDLR), transcript variant 1, mRNA
Homo sapiens low density lipoprotein receptor (LDLR), transcript variant 1, mRNA
gi|1732746181|ref|NM_000527.5|

Nucleotide
Chain C, Son of sevenless protein homolog 1
Chain C, Son of sevenless protein homolog 1
gi|56554476|pdb|1XD2|C

Protein
Chain B, Transforming protein p21/H-Ras-1
Chain B, Transforming protein p21/H-Ras-1
gi|56554475|pdb|1XD2|B

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001543308	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 27, 2020)	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

SCV001543308

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 27, 2020)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001543308.4

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

Description

This sequence change replaces glutamic acid with valine at codon 421 of the BRIP1 protein (p.Glu421Val). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, 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 29, 2024

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