2-214781468-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000465.4(BARD1):c.406G>T(p.Ala136Ser) 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 1,459,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BARD1 | NM_000465.4 | c.406G>T | p.Ala136Ser | missense_variant | 4/11 | ENST00000260947.9 | NP_000456.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BARD1 | ENST00000260947.9 | c.406G>T | p.Ala136Ser | missense_variant | 4/11 | 1 | NM_000465.4 | ENSP00000260947 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248646Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134332
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459844Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726130
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 2023 | The p.A136S variant (also known as c.406G>T), located in coding exon 4 of the BARD1 gene, results from a G to T substitution at nucleotide position 406. The alanine at codon 136 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 05, 2017 | This sequence change replaces alanine with serine at codon 136 of the BARD1 protein (p.Ala136Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BARD1-related disease. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at