2-47466674-A-T

Variant summary

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

The NM_000251.3(MSH2):​c.1527A>T​(p.Lys509Asn) variant causes a missense 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: 33)

Consequence

MSH2
NM_000251.3 missense

Scores

7
11
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.745
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.1527A>T p.Lys509Asn missense_variant 10/16 ENST00000233146.7 NP_000242.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MSH2ENST00000233146.7 linkuse as main transcriptc.1527A>T p.Lys509Asn missense_variant 10/161 NM_000251.3 ENSP00000233146 P1P43246-1

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.80
D;.;.;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Uncertain
0.27
D
MetaRNN
Uncertain
0.66
D;D;D;D
MetaSVM
Uncertain
0.61
D
MutationAssessor
Pathogenic
3.3
M;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-4.9
D;D;.;D
REVEL
Pathogenic
0.68
Sift
Pathogenic
0.0
D;D;.;D
Sift4G
Uncertain
0.0030
D;D;.;D
Polyphen
0.99
D;.;.;D
Vest4
0.83
MutPred
0.45
Loss of ubiquitination at K509 (P = 0.0107);.;Loss of ubiquitination at K509 (P = 0.0107);Loss of ubiquitination at K509 (P = 0.0107);
MVP
0.96
MPC
0.033
ClinPred
1.0
D
GERP RS
1.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.96
gMVP
0.66

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: chr2-47693813; API