2-47445653-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000251.3(MSH2):​c.1382A>T​(p.Asp461Val) variant causes a missense change. 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)

Consequence

MSH2
NM_000251.3 missense

Scores

7
10
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.93
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MSH2NM_000251.3 linkc.1382A>T p.Asp461Val missense_variant 8/16 ENST00000233146.7 NP_000242.1 P43246-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MSH2ENST00000233146.7 linkc.1382A>T p.Asp461Val missense_variant 8/161 NM_000251.3 ENSP00000233146.2 P43246-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.83
D;.;.;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.97
D;D;D;D
M_CAP
Uncertain
0.26
D
MetaRNN
Pathogenic
0.83
D;D;D;D
MetaSVM
Pathogenic
0.84
D
MutationAssessor
Uncertain
2.8
M;.;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-4.9
D;D;.;D
REVEL
Pathogenic
0.84
Sift
Uncertain
0.0020
D;D;.;D
Sift4G
Uncertain
0.012
D;D;.;D
Polyphen
0.79
P;.;.;P
Vest4
0.64
MutPred
0.59
Loss of disorder (P = 0.0204);.;Loss of disorder (P = 0.0204);Loss of disorder (P = 0.0204);
MVP
0.97
MPC
0.0060
ClinPred
0.99
D
GERP RS
4.4
Varity_R
0.84
gMVP
0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-47672792; COSMIC: COSV51880244; API