rs545546432
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_005732.4(RAD50):āc.63T>Gā(p.Asp21Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. D21N) has been classified as Uncertain significance.
Frequency
Consequence
NM_005732.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.63T>G | p.Asp21Glu | missense_variant | 1/25 | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.63T>G | p.Asp21Glu | missense_variant | 1/25 | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152256Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461708Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 727178
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152374Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74526
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2022 | The p.D21E variant (also known as c.63T>G), located in coding exon 1 of the RAD50 gene, results from a T to G substitution at nucleotide position 63. The aspartic acid at codon 21 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 21 of the RAD50 protein (p.Asp21Glu). This variant is present in population databases (rs545546432, gnomAD 0.01%). 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: 408398). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD50 protein function. 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. - |
Nijmegen breakage syndrome-like disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at