18-79801978-G-T

Position:

• chr18-79801978-G-T

Variant summary

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

The NM_012283.2(KCNG2):​c.-115+3964G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,162 control chromosomes in the GnomAD database, including 3,068 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 0.20 (3068 hom., cov: 33)
• Consequence: KCNG2 NM_012283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNG2	NM_012283.2	c.-115+3964G>T		intron_variant		ENST00000316249.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNG2	ENST00000316249.4	c.-115+3964G>T		intron_variant		1	NM_012283.2	P1
	ENST00000592499.2	n.76+9177G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29805 AN: 152044 Hom.: 3068 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.196 AC: 29831 AN: 152162 Hom.: 3068 Cov.: 33 AF XY: 0.194 AC XY: 14399 AN XY: 74384

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.196

Alfa AF: 0.196 Hom.: 2294

Bravo AF: 0.195

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.87
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8091998; hg19: chr18-77561978;