2-47403078-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001258281.1(MSH2):​c.-128G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

MSH2
NM_001258281.1 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.463
Variant links:
Genes affected
MSH2 (HGNC:7325): (mutS homolog 2) This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MSH2NM_001258281.1 linkc.-128G>C 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 17 NP_001245210.1 P43246-2
MSH2NM_001258281.1 linkc.-128G>C 5_prime_UTR_variant Exon 1 of 17 NP_001245210.1 P43246-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MSH2ENST00000543555 linkc.-128G>C 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 17 2 ENSP00000442697.1 P43246-2
MSH2ENST00000543555 linkc.-128G>C 5_prime_UTR_variant Exon 1 of 17 2 ENSP00000442697.1 P43246-2
MSH2ENST00000645506.1 linkc.-114G>C upstream_gene_variant ENSP00000495455.1 A0A2R8Y6P0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
12
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
12
DANN
Benign
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs786203146; hg19: chr2-47630217; API