rs374561375
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_005732.4(RAD50):c.260G>A(p.Arg87His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,602,258 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87C) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.260G>A | p.Arg87His | missense_variant | 3/25 | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.260G>A | p.Arg87His | missense_variant | 3/25 | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000546 AC: 83AN: 152138Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000660 AC: 166AN: 251340Hom.: 1 AF XY: 0.000758 AC XY: 103AN XY: 135842
GnomAD4 exome AF: 0.000293 AC: 425AN: 1450002Hom.: 3 Cov.: 31 AF XY: 0.000382 AC XY: 276AN XY: 722022
GnomAD4 genome ? AF: 0.000545 AC: 83AN: 152256Hom.: 1 Cov.: 32 AF XY: 0.000699 AC XY: 52AN XY: 74432
ClinVar
Submissions by phenotype
Nijmegen breakage syndrome-like disorder Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 19, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 19, 2017 | - - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 08, 2020 | - - |
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 13, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 10, 2016 | - - |
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | May 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in individuals with breast cancer (Damiola 2014, Couch 2015, Maxwell 2015); This variant is associated with the following publications: (PMID: 25452441, 25503501, 24894818) - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2022 | This alteration is classified as likely 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at