NM_000465.4(BARD1):c.1931T>G (p.Val644Gly) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 8, 2018
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:: RCV000794447.8

Allele description [Variation Report for NM_000465.4(BARD1):c.1931T>G (p.Val644Gly)]

NM_000465.4(BARD1):c.1931T>G (p.Val644Gly)

Gene:

BARD1:BRCA1 associated RING domain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_000465.4(BARD1):c.1931T>G (p.Val644Gly)

HGVS:

NC_000002.12:g.214730481A>C
NG_012047.3:g.84231T>G
NM_000465.4:c.1931T>GMANE SELECT
NM_001282543.2:c.1874T>G
NM_001282545.2:c.578T>G
NM_001282548.2:c.521T>G
NM_001282549.2:c.392T>G
NP_000456.2:p.Val644Gly
NP_001269472.1:p.Val625Gly
NP_001269474.1:p.Val193Gly
NP_001269477.1:p.Val174Gly
NP_001269478.1:p.Val131Gly
LRG_297t1:c.1931T>G
LRG_297:g.84231T>G
LRG_297p1:p.Val644Gly
NC_000002.11:g.215595205A>C
NG_012047.2:g.84224T>G
NM_000465.3:c.1931T>G
NR_104212.2:n.1896T>G
NR_104215.2:n.1839T>G
NR_104216.2:n.1095T>G

Protein change:

V131G

Links:

dbSNP: rs1574707186

NCBI 1000 Genomes Browser:

rs1574707186

Molecular consequence:

NM_000465.4:c.1931T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.1874T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.578T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.521T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.392T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.1896T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.1839T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.1095T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

Recent activity

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Mus musculus receptor tyrosine kinase-like orphan receptor 1 (Ror1), mRNA
Mus musculus receptor tyrosine kinase-like orphan receptor 1 (Ror1), mRNA
gi|31560492|ref|NM_013845.2|

Nucleotide
GEO Profiles Links for Nucleotide (Select 4101586) (1000)
GEO Profiles
PAK4 p21 (RAC1) activated kinase 4 [Homo sapiens]
PAK4 p21 (RAC1) activated kinase 4 [Homo sapiens]
Gene ID:10298

Gene
Gene Links for Nucleotide (Select 4101586) (1)
Gene
dbVar for Gene (Select 2298) (365)
dbVar

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000933856	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 8, 2018)	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

SCV000933856

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 8, 2018)

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, SCV000933856.4

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

Description

This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BARD1-related disease. This sequence change replaces valine with glycine at codon 644 of the BARD1 protein (p.Val644Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine.

#	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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