2-47403082-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001258281.1(MSH2):c.-124G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000105 in 951,760 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 -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSH2 | ENST00000543555 | c.-124G>A | 5_prime_UTR_variant | Exon 1 of 17 | 2 | ENSP00000442697.1 | ||||
MSH2 | ENST00000406134.5 | c.-110G>A | upstream_gene_variant | 1 | ENSP00000384199.1 | |||||
MSH2 | ENST00000645506.1 | c.-110G>A | upstream_gene_variant | ENSP00000495455.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000105 AC: 1AN: 951760Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0AN XY: 486066
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The c.-110G>A variant is located in the 5' untranslated region (5’ UTR) of the MSH2 gene. This variant results from a G to A substitution 110 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; however 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 poorly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at