5-132595694-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_005732.4(RAD50):c.2091C>T(p.Val697Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,613,774 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_005732.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.2091C>T | p.Val697Val | synonymous_variant | Exon 13 of 25 | 1 | NM_005732.4 | ENSP00000368100.4 | ||
ENSG00000283782 | ENST00000640655.2 | c.1794C>T | p.Val598Val | synonymous_variant | Exon 14 of 26 | 5 | ENSP00000491596.2 |
Frequencies
GnomAD3 genomes AF: 0.00152 AC: 231AN: 152120Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.000366 AC: 92AN: 251302Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135814
GnomAD4 exome AF: 0.000153 AC: 224AN: 1461536Hom.: 1 Cov.: 30 AF XY: 0.000113 AC XY: 82AN XY: 727096
GnomAD4 genome AF: 0.00154 AC: 235AN: 152238Hom.: 3 Cov.: 32 AF XY: 0.00142 AC XY: 106AN XY: 74442
ClinVar
Submissions by phenotype
Nijmegen breakage syndrome-like disorder Benign:3
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not specified Benign:2
Variant summary: The RAD50 c.2091C>T (p.Val697Val) variant involves the alteration of a non-conserved nucleotide causes a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 129/277028 control chromosomes (gnomAD), predominantly observed in the African subpopulation at a frequency of 0.004827 (116/24030). This frequency is about 77 times the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. A publication, Young_2016, cites the variant, however, with limited information. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign. -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Hereditary cancer-predisposing syndrome Benign:2
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 Benign:1
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Familial cancer of breast Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at