rs1057518894
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000465.4(BARD1):āc.1463A>Gā(p.Asn488Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N488D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000465.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BARD1 | NM_000465.4 | c.1463A>G | p.Asn488Ser | missense_variant | 6/11 | ENST00000260947.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BARD1 | ENST00000260947.9 | c.1463A>G | p.Asn488Ser | missense_variant | 6/11 | 1 | NM_000465.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251338Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135832
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461756Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727182
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 19, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2023 | The p.N488S variant (also known as c.1463A>G), located in coding exon 6 of the BARD1 gene, results from an A to G substitution at nucleotide position 1463. The asparagine at codon 488 is replaced by serine, an amino acid with highly similar properties. This alteration was found to have intermediate activity in a homology-directed DNA repair (HDR) assay (Adamovich AI et al. PLoS Genet, 2019 03;15:e1008049). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2019 | - - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 11, 2023 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 488 of the BARD1 protein (p.Asn488Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 374093). 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 disruptive. Experimental studies have shown that this missense change does not substantially affect BARD1 function (PMID: 30925164). 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. - |
Hereditary cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jun 04, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at