18-79813548-A-G

Position:

• chr18-79813548-A-G

Variant summary

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

The NM_012283.2(KCNG2):​c.-115+15534A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,098 control chromosomes in the GnomAD database, including 10,089 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 0.35 (10089 hom., cov: 33)
• Consequence: KCNG2 NM_012283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

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]

ENSG00000267780 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNG2	NM_012283.2	c.-115+15534A>G		intron_variant		ENST00000316249.4	NP_036415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNG2	ENST00000316249.4	c.-115+15534A>G		intron_variant		1	NM_012283.2	ENSP00000315654.3
ENSG00000267780	ENST00000592499.2	n.77-2531A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53769 AN: 151980 Hom.: 10059 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.354 AC: 53867 AN: 152098 Hom.: 10089 Cov.: 33 AF XY: 0.360 AC XY: 26768 AN XY: 74360

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.333

Alfa AF: 0.289 Hom.: 14894

Bravo AF: 0.360

Asia WGS AF: 0.503 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4799088; hg19: chr18-77573548;