rs752387348
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000251.3(MSH2):c.282G>A(p.Leu94=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L94L) has been classified as Likely benign.
Frequency
Consequence
NM_000251.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH2 | NM_000251.3 | c.282G>A | p.Leu94= | synonymous_variant | 2/16 | ENST00000233146.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH2 | ENST00000233146.7 | c.282G>A | p.Leu94= | synonymous_variant | 2/16 | 1 | NM_000251.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251238Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135790
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460162Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726470
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hereditary nonpolyposis colorectal neoplasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2019 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with MSH2-related disease. This variant is present in population databases (rs752387348, ExAC 0.001%). This sequence change affects codon 94 of the MSH2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MSH2 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at