18-79864479-G-A

Position:

• chr18-79864479-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012283.2(KCNG2):​c.624+188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,020 control chromosomes in the GnomAD database, including 1,024 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1024 hom., cov: 32)
• Consequence: KCNG2 NM_012283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNG2	NM_012283.2	c.624+188G>A		intron_variant		ENST00000316249.4	NP_036415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNG2	ENST00000316249.4	c.624+188G>A		intron_variant		1	NM_012283.2	ENSP00000315654	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16519 AN: 151908 Hom.: 1025 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.0603

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16516 AN: 152020 Hom.: 1024 Cov.: 32 AF XY: 0.104 AC XY: 7757 AN XY: 74288

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0355

Gnomad4 SAS AF: 0.0601

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.133

Alfa AF: 0.120 Hom.: 141

Bravo AF: 0.111

Asia WGS AF: 0.0560 AC: 195 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.40
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs62103177; hg19: chr18-77624479;