2-47403093-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001258281.1(MSH2):c.-113C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,297,434 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 (★).
Frequency
Consequence
NM_001258281.1 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSH2 | ENST00000543555 | c.-113C>G | 5_prime_UTR_variant | Exon 1 of 17 | 2 | ENSP00000442697.1 | ||||
MSH2 | ENST00000406134.5 | c.-99C>G | upstream_gene_variant | 1 | ENSP00000384199.1 | |||||
MSH2 | ENST00000645506.1 | c.-99C>G | upstream_gene_variant | ENSP00000495455.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000873 AC: 10AN: 1145110Hom.: 0 Cov.: 16 AF XY: 0.0000122 AC XY: 7AN XY: 575168
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74492
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The c.-99C>G variant is located in the 5' untranslated region (5’ UTR) of the MSH2 gene. This variant results from a C to G substitution 99 bases upstream from the first translated codon. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. This position was not covered in the ESP. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 115000 alleles tested) in our clinical cohort. This nucleotide position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of c.-99C>G remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at