rs17217709

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001258281.1(MSH2):​c.-116T>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 0.0000183 in 1,092,738 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

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MSH2
NM_001258281.1 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.479
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MSH2NM_001258281.1 linkuse as main transcriptc.-116T>A 5_prime_UTR_variant 1/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MSH2ENST00000543555.6 linkuse as main transcriptc.-116T>A 5_prime_UTR_variant 1/172 P43246-2
MSH2ENST00000406134.5 linkuse as main transcript upstream_gene_variant 1
MSH2ENST00000645506.1 linkuse as main transcript upstream_gene_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000183
AC:
20
AN:
1092738
Hom.:
0
Cov.:
15
AF XY:
0.0000200
AC XY:
11
AN XY:
551354
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000245
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 31, 2018The c.-102T>A variant is located in the 5' untranslated region (5’ UTR) of the MSH2 gene. This variant results from a T to A substitution 102 bases upstream from the first translated codon. This nucleotide position is not well conserved in available vertebrate species, and adenine is the reference nucleotide in many species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
2.7
DANN
Benign
0.70

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: rs17217709; hg19: chr2-47630229; API