chr5-132588087-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005732.4(RAD50):c.1049A>G(p.Gln350Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000311 in 1,609,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on 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. Q350H) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.1049A>G | p.Gln350Arg | missense_variant, splice_region_variant | 7/25 | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.1049A>G | p.Gln350Arg | missense_variant, splice_region_variant | 7/25 | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250464Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135396
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1457478Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725216
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2022 | The p.Q350R variant (also known as c.1049A>G), located in coding exon 7 of the RAD50 gene, results from an A to G substitution at nucleotide position 1049. The glutamine at codon 350 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. 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 10, 2023 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 350 of the RAD50 protein (p.Gln350Arg). This variant is present in population databases (rs751434866, gnomAD 0.006%). 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: 571246). 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 tolerated. 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 | Dec 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at