Variant 18-79863774-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000316249.4(KCNG2):c.107C>T(p.Ala36Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,269,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

KCNG2
ENST00000316249.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95

Variant links:

Genes affected

KCNG2 (HGNC:6249): (potassium voltage-gated channel modifier subfamily G member 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily G. This member is a gamma subunit of the voltage-gated potassium channel. The delayed-rectifier type channels containing this subunit may contribute to cardiac action potential repolarization. [provided by RefSeq, Jul 2008]

KCNG2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2912674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNG2	NM_012283.2 linkuse as main transcript	c.107C>T	p.Ala36Val	missense_variant	3/4	ENST00000316249.4	NP_036415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNG2	ENST00000316249.4 linkuse as main transcript	c.107C>T	p.Ala36Val	missense_variant	3/4	1	NM_012283.2	ENSP00000315654	P1

Frequencies

GnomAD3 genomes

AF:

0.000548

AC:

AN:

149762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000400

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

9244

Hom.:

AF XY:

0.000172

AC XY:

AN XY:

5830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00463

GnomAD4 exome

AF:

0.0000589

AC:

AN:

1119788

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

540404

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.000919

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000254

GnomAD4 genome

AF:

0.000554

AC:

AN:

149868

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

AN XY:

73172

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.000399

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.000793

ExAC

AF:

0.0000538

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2021

The c.107C>T (p.A36V) alteration is located in exon 1 (coding exon 1) of the KCNG2 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the alanine (A) at amino acid position 36 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.82

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.1

REVEL

Benign

0.21

Sift

Uncertain

0.0040

Sift4G

Benign

0.067

Polyphen

0.80

Vest4

0.21

MutPred

0.46

Gain of MoRF binding (P = 0.0902);

MVP

0.82

MPC

2.0

ClinPred

0.26

GERP RS

1.3

Varity_R

0.095

gMVP

0.41

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