chr5-132588018-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_005732.4(RAD50):c.980G>A(p.Arg327His) variant causes a missense change. The variant allele was found at a frequency of 0.00257 in 1,611,958 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005732.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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RAD50 | ENST00000378823.8 | c.980G>A | p.Arg327His | missense_variant | Exon 7 of 25 | 1 | NM_005732.4 | ENSP00000368100.4 | ||
ENSG00000283782 | ENST00000640655.2 | c.683G>A | p.Arg228His | missense_variant | Exon 8 of 26 | 5 | ENSP00000491596.2 |
Frequencies
GnomAD3 genomes AF: 0.00225 AC: 342AN: 152168Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00346 AC: 865AN: 249856Hom.: 3 AF XY: 0.00394 AC XY: 533AN XY: 135142
GnomAD4 exome AF: 0.00261 AC: 3806AN: 1459672Hom.: 24 Cov.: 31 AF XY: 0.00288 AC XY: 2092AN XY: 726296
GnomAD4 genome AF: 0.00224 AC: 341AN: 152286Hom.: 1 Cov.: 32 AF XY: 0.00219 AC XY: 163AN XY: 74458
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:4
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
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not provided Uncertain:1Benign:2
This variant is associated with the following publications: (PMID: 29928469, 16385572, 27153395, 20805886, 31159747) -
RAD50: BP4, BS2 -
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Nijmegen breakage syndrome-like disorder Uncertain:1Benign:1
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not specified Benign:2
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RAD50-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at