rs886055600
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000465.4(BARD1):c.245G>T(p.Gly82Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G82A) has been classified as Likely benign.
Frequency
Consequence
NM_000465.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BARD1 | NM_000465.4 | c.245G>T | p.Gly82Val | missense_variant | 3/11 | ENST00000260947.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BARD1 | ENST00000260947.9 | c.245G>T | p.Gly82Val | missense_variant | 3/11 | 1 | NM_000465.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249596Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134912
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459790Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726090
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
Familial cancer of breast Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 18, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. ClinVar contains an entry for this variant (Variation ID: 334195). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 82 of the BARD1 protein (p.Gly82Val). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 05, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 20, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 16, 2021 | This missense variant replaces glycine with valine at codon 82 of the BARD1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/249596 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Breast neoplasm Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at