rs200264387
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_005732.4(RAD50):c.885+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005732.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.885+5G>A | splice_region_variant, intron_variant | 1 | NM_005732.4 | ENSP00000368100.4 | ||||
ENSG00000283782 | ENST00000640655.2 | c.588+5G>A | splice_region_variant, intron_variant | 5 | ENSP00000491596.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000599 AC: 15AN: 250534Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135664
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461304Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 726974
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74466
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2023 | The c.885+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 6 in the RAD50 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 20, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 12, 2024 | The RAD50 c.885+5G>A variant has been reported in the published literature in a case-control study of breast cancer. However, it was not specified whether the variant was identified in an individual with breast cancer or a reportedly healthy individual (PMID: 26787654 (2016)). The frequency of this variant in the general population, 0.00038 (13/34550 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant may affect proper RAD50 mRNA splicing. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Nijmegen breakage syndrome-like disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 28, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at