rs2230017
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_005732.4(RAD50):c.572C>T(p.Thr191Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,612,294 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T191T) has been classified as Likely benign.
Frequency
Consequence
NM_005732.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.572C>T | p.Thr191Ile | missense_variant | 5/25 | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.572C>T | p.Thr191Ile | missense_variant | 5/25 | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00432 AC: 657AN: 152100Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00145 AC: 363AN: 250440Hom.: 3 AF XY: 0.00117 AC XY: 159AN XY: 135432
GnomAD4 exome AF: 0.000665 AC: 971AN: 1460076Hom.: 3 Cov.: 31 AF XY: 0.000585 AC XY: 425AN XY: 726454
GnomAD4 genome AF: 0.00433 AC: 659AN: 152218Hom.: 6 Cov.: 32 AF XY: 0.00433 AC XY: 322AN XY: 74416
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 08, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2013 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 11, 2014 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 29, 2016 | Variant summary: The RAD50 c.572C>T (p.Thr191Ile) variant involves the alteration of a conserved nucleotide. 3/3 in silico tools predict a damaging outcome for this variant; however they are not definitive and the predictions have yet to be confirmed by published functional studies. This variant was found in 210/119642 control chromosomes (1 homozygote), predominantly observed in the African subpopulation at a frequency of 0.0147207 (146/9918). This frequency is about 236 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 large case-control study that used 2,984 breast cancer cases and 7,545 controls did not find an elevated risk for breast cancer due to this variant; instead, a protective effect was observed (OR: 0.44; p=0.0069) (Haiman_2013). In addition, multiple clinical diagnostic laboratories have classified this variant as benign/likely benign. Taken together, this variant is classified as Benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 24, 2017 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 25, 2014 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Familial cancer of breast Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Nijmegen breakage syndrome-like disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Counsyl | Aug 09, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at