chr18-79864479-G-A

Variant names:

• chr18-79864479-G-A
• rs62103177
• NM_012283.2:c.624+188G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNG2	NM_012283.2	c.624+188G>A		intron_variant	Intron 3 of 3	ENST00000316249.4	NP_036415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNG2	ENST00000316249.4	c.624+188G>A		intron_variant	Intron 3 of 3	1	NM_012283.2	ENSP00000315654.3

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

African (AFR) AF: 0.0689 AC: 2861 AN: 41532

American (AMR) AF: 0.105 AC: 1600 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3468

East Asian (EAS) AF: 0.0355 AC: 183 AN: 5148

South Asian (SAS) AF: 0.0601 AC: 290 AN: 4822

European-Finnish (FIN) AF: 0.0812 AC: 857 AN: 10554

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.142 AC: 9662 AN: 67906

Other (OTH) AF: 0.133 AC: 280 AN: 2106

Alfa AF: 0.134 Hom.: 1744

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
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62103177; hg19: chr18-77624479;