rs786203372
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_005732.4(RAD50):c.1967G>A(p.Arg656Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000096 in 1,457,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. 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. R656L) has been classified as Uncertain significance.
Frequency
Consequence
NM_005732.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.1967G>A | p.Arg656Gln | missense_variant, splice_region_variant | 12/25 | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.1967G>A | p.Arg656Gln | missense_variant, splice_region_variant | 12/25 | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000960 AC: 14AN: 1457872Hom.: 0 Cov.: 30 AF XY: 0.00000965 AC XY: 7AN XY: 725564
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2023 | The p.R656Q variant (also known as c.1967G>A), located in coding exon 12 of the RAD50 gene, results from a G to A substitution at nucleotide position 1967. The arginine at codon 656 is replaced by glutamine, an amino acid with highly similar properties. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 656 of the RAD50 protein (p.Arg656Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 186977). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at