dbSNP rs1114167845: MSH2:p.Gln314Lys (chr2-47414416-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000251.3(MSH2):c.940C>A(p.Gln314Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q314Q) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSH2
NM_000251.3 missense, splice_region

Scores

Splicing: ADA: 0.8088

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.59

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]

MSH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3 link	c.940C>A	p.Gln314Lys	missense_variant, splice_region_variant	Exon 5 of 16	ENST00000233146.7	NP_000242.1	P43246-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7 link	c.940C>A	p.Gln314Lys	missense_variant, splice_region_variant	Exon 5 of 16	1	NM_000251.3	ENSP00000233146.2		P43246-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

45208

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000914

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000373

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000210

AC:

AN:

438710

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

AN XY:

230554

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000217

Gnomad4 SAS exome

AF:

0.0000706

Gnomad4 FIN exome

AF:

0.0000398

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000334

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000442

AC:

AN:

45234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

19878

show subpopulations

Gnomad4 AFR

AF:

0.0000913

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000373

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;.;.;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Uncertain

0.57

MutationAssessor

Benign

2.0

M;.;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.98

N;N;.;N

REVEL

Pathogenic

0.77

Sift

Uncertain

0.015

D;D;.;D

Sift4G

Uncertain

0.034

D;D;.;D

Polyphen

0.27

B;.;.;P

Vest4

0.80

MutPred

0.58

Gain of ubiquitination at Q314 (P = 0.0238);.;Gain of ubiquitination at Q314 (P = 0.0238);Gain of ubiquitination at Q314 (P = 0.0238);

MVP

0.96

MPC

0.013

ClinPred

0.96

GERP RS

5.0

Varity_R

0.51

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.81

dbscSNV1_RF

Pathogenic

0.78

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over