rs758403441

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001406656.1(MSH2):​c.-90C>A 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 29)

Consequence

MSH2
NM_001406656.1 5_prime_UTR_premature_start_codon_gain

Scores

1
11
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.157
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MSH2NM_000251.3 linkuse as main transcriptc.808C>A p.Leu270Met missense_variant 5/16 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.808C>A p.Leu270Met missense_variant 5/161 NM_000251.3 ENSP00000233146.2 P43246-1

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.68
D;.;.;.
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.31
N
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Uncertain
0.093
D
MetaRNN
Uncertain
0.52
D;D;D;D
MetaSVM
Uncertain
0.63
D
MutationAssessor
Uncertain
2.8
M;.;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.96
N;N;.;N
REVEL
Uncertain
0.63
Sift
Benign
0.081
T;T;.;T
Sift4G
Uncertain
0.056
T;T;.;T
Polyphen
1.0
D;.;.;D
Vest4
0.65
MutPred
0.59
Gain of catalytic residue at L270 (P = 0.0102);.;Gain of catalytic residue at L270 (P = 0.0102);Gain of catalytic residue at L270 (P = 0.0102);
MVP
0.88
MPC
0.036
ClinPred
0.98
D
GERP RS
-0.12
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.43
gMVP
0.42

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: chr2-47641423; API