2-47403229-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000251.3(MSH2):​c.38G>T​(p.Ser13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MSH2
NM_000251.3 missense

Scores

3
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.23
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MSH2NM_000251.3 linkuse as main transcriptc.38G>T p.Ser13Ile missense_variant 1/16 ENST00000233146.7 NP_000242.1 P43246-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MSH2ENST00000233146.7 linkuse as main transcriptc.38G>T p.Ser13Ile missense_variant 1/161 NM_000251.3 ENSP00000233146.2 P43246-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1448044
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
719192
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.36
T;.;.
Eigen
Benign
0.014
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.87
D;D;D
MetaSVM
Uncertain
0.13
D
MutationAssessor
Benign
0.68
N;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.6
N;.;N
REVEL
Uncertain
0.55
Sift
Benign
0.20
T;.;T
Sift4G
Benign
0.20
T;.;T
Polyphen
0.0
B;.;P
Vest4
0.70
MutPred
0.78
Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);Loss of disorder (P = 0.0109);
MVP
0.98
MPC
0.0062
ClinPred
0.60
D
GERP RS
5.5
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.7
Varity_R
0.53
gMVP
0.50

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: rs63749907; hg19: chr2-47630368; API