2-47463139-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000251.3(MSH2):c.1495G>T(p.Ala499Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000251.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MSH2 | NM_000251.3 | c.1495G>T | p.Ala499Ser | missense_variant | 9/16 | ENST00000233146.7 | NP_000242.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSH2 | ENST00000233146.7 | c.1495G>T | p.Ala499Ser | missense_variant | 9/16 | 1 | NM_000251.3 | ENSP00000233146.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461676Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727146
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary nonpolyposis colorectal neoplasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 14, 2023 | 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. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 499 of the MSH2 protein (p.Ala499Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.