rs786203417
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000465.4(BARD1):c.266C>G(p.Pro89Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,611,884 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P89L) has been classified 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BARD1 | NM_000465.4 | c.266C>G | p.Pro89Arg | missense_variant | 3/11 | ENST00000260947.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BARD1 | ENST00000260947.9 | c.266C>G | p.Pro89Arg | missense_variant | 3/11 | 1 | NM_000465.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000663 AC: 1AN: 150782Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250924Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135640
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461102Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726832
GnomAD4 genome ? AF: 0.00000663 AC: 1AN: 150782Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1AN XY: 73496
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 23, 2022 | The p.P89R variant (also known as c.266C>G), located in coding exon 3 of the BARD1 gene, results from a C to G substitution at nucleotide position 266. The proline at codon 89 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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 | Invitae | Aug 06, 2023 | 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 0.007%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 89 of the BARD1 protein (p.Pro89Arg). ClinVar contains an entry for this variant (Variation ID: 482790). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at