Variant 2-47512439-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000327876.5(KCNK12):c.*8468C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,597,042 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 7 hom. )

Consequence

KCNK12
ENST00000327876.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

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:

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-47512439-G-C is Benign according to our data. Variant chr2-47512439-G-C is described in ClinVar as [Benign]. Clinvar id is 927126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 225 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK12	NM_022055.2 linkuse as main transcript	c.*8468C>G		3_prime_UTR_variant	2/2	ENST00000327876.5	NP_071338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK12	ENST00000327876.5 linkuse as main transcript	c.*8468C>G		3_prime_UTR_variant	2/2	1	NM_022055.2	ENSP00000327611	P1

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

226

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00217

AC:

477

AN:

219438

Hom.:

AF XY:

0.00227

AC XY:

272

AN XY:

119754

show subpopulations

Gnomad AFR exome

AF:

0.000844

Gnomad AMR exome

AF:

0.00172

Gnomad ASJ exome

AF:

0.00914

Gnomad EAS exome

AF:

0.0000612

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.00262

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.00362

GnomAD4 exome

AF:

0.00153

AC:

2213

AN:

1444732

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1160

AN XY:

716920

show subpopulations

Gnomad4 AFR exome

AF:

0.000758

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00915

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00284

Gnomad4 FIN exome

AF:

0.00209

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.00273

GnomAD4 genome

AF:

0.00148

AC:

225

AN:

152310

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00236

Hom.:

Bravo

AF:

0.00149

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	MSH2: BP4, BS1, BS2 -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Oct 27, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.32

DANN

Benign

0.61

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