rs786201698
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The variant allele was found at a frequency of 0.0000683 in 687,918 control chromosomes in the GnomAD database, including 1 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
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152262Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000766 AC: 41AN: 535538Hom.: 1 Cov.: 6 AF XY: 0.0000595 AC XY: 17AN XY: 285908
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152380Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74514
ClinVar
Submissions by phenotype
MSH2-related disorder Uncertain:1
The MSH2 c.-181G>A variant is located in the 5' untranslated region. This variant has been reported in a patient with sporadic early onset colorectal cancer and was found to decrease transcriptional efficiency (reported 77% decrease) (Shin et al. 2002. PubMed ID: 11782355). This variant is reported in 0.13% of alleles in individuals of East Asian descent in gnomAD and is listed in ClinVar as a variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/184792/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Lynch syndrome 1 Uncertain:1
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not provided Uncertain:1
Observed in individuals with early-onset colorectal cancer showing microsatellite instability (Shin et al., 2002); Published functional studies are inconclusive: showed significantly decreased promoter activity compared to wild-type in a luciferase assay, but did not affect DNA binding activity of nuclear factors (Shin et al., 2002); Nucleotide substitution is not conserved across species; Also known as c.-190G>A; This variant is associated with the following publications: (PMID: 11782355, 36577833) -
Hereditary nonpolyposis colorectal neoplasms Uncertain:1
This variant occurs in a non-coding region of the MSH2 gene. It does not change the encoded amino acid sequence of the MSH2 protein. This variant is present in population databases (rs786201698, gnomAD 0.1%). This variant has been observed in individual(s) with colorectal cancer (PMID: 11782355). This variant is also known as -190G>A. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on MSH2 function (PMID: 11782355). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Muir-Torré syndrome;C2936783:Lynch syndrome 1;C5436806:Mismatch repair cancer syndrome 2 Uncertain:1
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Hereditary cancer-predisposing syndrome Benign:1
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