NM_000465.4(BARD1):c.1973G>A (p.Arg658His) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 29, 2024
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:: RCV000228912.14

Allele description [Variation Report for NM_000465.4(BARD1):c.1973G>A (p.Arg658His)]

NM_000465.4(BARD1):c.1973G>A (p.Arg658His)

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.1973G>A (p.Arg658His)

Other names:

NP_000456.2:p.Arg658His

HGVS:

NC_000002.12:g.214730439C>T
NG_012047.3:g.84273G>A
NM_000465.4:c.1973G>AMANE SELECT
NM_001282543.2:c.1916G>A
NM_001282545.2:c.620G>A
NM_001282548.2:c.563G>A
NM_001282549.2:c.434G>A
NP_000456.2:p.Arg658His
NP_001269472.1:p.Arg639His
NP_001269474.1:p.Arg207His
NP_001269477.1:p.Arg188His
NP_001269478.1:p.Arg145His
LRG_297t1:c.1973G>A
LRG_297:g.84273G>A
LRG_297p1:p.Arg658His
NC_000002.11:g.215595163C>T
NG_012047.2:g.84266G>A
NM_000465.2:c.1973G>A
NM_000465.3:c.1973G>A
NR_104212.2:n.1938G>A
NR_104215.2:n.1881G>A
NR_104216.2:n.1137G>A

Protein change:

R145H

Links:

dbSNP: rs377227840

NCBI 1000 Genomes Browser:

rs377227840

Molecular consequence:

NM_000465.4:c.1973G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.1916G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.620G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.563G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.434G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.1938G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.1881G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.1137G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000284936	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 29, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29769598, 35264596, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000284936

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 29, 2024)

germline

clinical testing

PubMed (3)
[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

Germline mutation in the TP53 gene in uveal melanoma.

Hajkova N, Hojny J, Nemejcova K, Dundr P, Ulrych J, Jirsova K, Glezgova J, Ticha I.

Sci Rep. 2018 May 16;8(1):7618. doi: 10.1038/s41598-018-26040-0.

PubMed [citation]

PMID:: 29769598
PMCID:: PMC5955881

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Guindalini RSC, Viana DV, Kitajima JPFW, Rocha VM, López RVM, Zheng Y, Freitas É, Monteiro FPM, Valim A, Schlesinger D, Kok F, Olopade OI, Folgueira MAAK.

Sci Rep. 2022 Mar 9;12(1):4190. doi: 10.1038/s41598-022-07383-1.

PubMed [citation]

PMID:: 35264596
PMCID:: PMC8907244

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000284936.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 658 of the BARD1 protein (p.Arg658His). This variant is present in population databases (rs377227840, gnomAD 0.03%). This missense change has been observed in individual(s) with breast cancer and/or uveal melanoma (PMID: 29769598, 35264596). ClinVar contains an entry for this variant (Variation ID: 230212). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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: Oct 13, 2024

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