Variant 2-47521249-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000327876.5(KCNK12):c.951C>T(p.Cys317=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,606,892 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 16 hom. )

Consequence

KCNK12
ENST00000327876.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.44

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 2-47521249-G-A is Benign according to our data. Variant chr2-47521249-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 723795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.44 with no splicing effect.

BS2

High AC in GnomAd4 at 328 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK12	NM_022055.2 linkuse as main transcript	c.951C>T	p.Cys317=	synonymous_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.951C>T	p.Cys317=	synonymous_variant	2/2	1	NM_022055.2	ENSP00000327611	P1

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

328

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00355

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00278

AC:

648

AN:

233154

Hom.:

AF XY:

0.00287

AC XY:

367

AN XY:

127890

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00384

Gnomad ASJ exome

AF:

0.000928

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00247

Gnomad FIN exome

AF:

0.000442

Gnomad NFE exome

AF:

0.00365

Gnomad OTH exome

AF:

0.00596

GnomAD4 exome

AF:

0.00315

AC:

4580

AN:

1454680

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

2282

AN XY:

723128

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.00379

Gnomad4 ASJ exome

AF:

0.00104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.000664

Gnomad4 NFE exome

AF:

0.00347

Gnomad4 OTH exome

AF:

0.00385

GnomAD4 genome

AF:

0.00215

AC:

328

AN:

152212

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00355

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00238

Hom.:

Bravo

AF:

0.00225

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	KCNK12: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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