Variant ENST00000406134.5:c.2744A>G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000406134.5(MSH2):c.2744A>G(p.Gln915Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,608,286 control chromosomes in the GnomAD database, including 131,626 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 17425 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114201 hom. )

Consequence

MSH2
ENST00000406134.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2O:1

Conservation

PhyloP100: 0.310

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:

KCNK12 (HGNC:6274): (potassium two pore domain channel subfamily K member 12) This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The product of this gene has not been shown to be a functional channel, however, it may require other non-pore-forming proteins for activity. [provided by RefSeq, Jul 2008]

KCNK12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0538463E-6).

BP6

Variant 2-47512412-A-G is Benign according to our data. Variant chr2-47512412-A-G is described in ClinVar as [Benign]. Clinvar id is 41867.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-47512412-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK12	NM_022055.2 link	c.*8495T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000327876.5	NP_071338.1	Q9HB15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK12	ENST00000327876 link	c.*8495T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_022055.2	ENSP00000327611.3		Q9HB15

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70244

AN:

151836

Hom.:

17404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.522

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.658

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.424

GnomAD3 exomes

AF:

0.421

AC:

98765

AN:

234612

Hom.:

21907

AF XY:

0.418

AC XY:

53728

AN XY:

128676

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.337

Gnomad EAS exome

AF:

0.682

Gnomad SAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.390

AC:

568429

AN:

1456328

Hom.:

114201

Cov.:

AF XY:

0.391

AC XY:

282997

AN XY:

723972

show subpopulations

Gnomad4 AFR exome

AF:

0.620

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.621

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.419

GnomAD4 genome

AF:

0.463

AC:

70321

AN:

151958

Hom.:

17425

Cov.:

AF XY:

0.466

AC XY:

34602

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.614

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.657

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.499

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.424

Alfa

AF:

0.389

Hom.:

5755

Bravo

AF:

0.459

TwinsUK

AF:

0.362

AC:

1343

ALSPAC

AF:

0.360

AC:

1388

ESP6500AA

AF:

0.583

AC:

1021

ESP6500EA

AF:

0.362

AC:

1440

ExAC

AF:

0.422

AC:

48866

Asia WGS

AF:

0.548

AC:

1904

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2012

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: research

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.87

DANN

Benign

0.43

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.24

T;T

MetaRNN

Benign

0.0000071

T;T

MetaSVM

Benign

-0.97

PROVEAN

Benign

-0.37

.;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.65

.;T

Polyphen

0.0

.;B

Vest4

0.015

ClinPred

0.0050

GERP RS

-3.0

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over