NM_012283.2:c.-115+21759G>A

Variant names:

• chr18-79819773-G-A
• rs7236339
• NM_012283.2:c.-115+21759G>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.-115+21759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,212 control chromosomes in the GnomAD database, including 2,872 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 0.19 (2872 hom., cov: 33)
• Consequence: KCNG2 NM_012283.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 9 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 = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNG2	NM_012283.2	c.-115+21759G>A		intron_variant	Intron 1 of 3	ENST00000316249.4	NP_036415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNG2	ENST00000316249.4	c.-115+21759G>A		intron_variant	Intron 1 of 3	1	NM_012283.2	ENSP00000315654.3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29246 AN: 152094 Hom.: 2871 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.192 AC: 29271 AN: 152212 Hom.: 2872 Cov.: 33 AF XY: 0.190 AC XY: 14107 AN XY: 74422

African (AFR) AF: 0.162 AC: 6711 AN: 41532

American (AMR) AF: 0.173 AC: 2648 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3470

East Asian (EAS) AF: 0.102 AC: 528 AN: 5176

South Asian (SAS) AF: 0.118 AC: 568 AN: 4826

European-Finnish (FIN) AF: 0.249 AC: 2632 AN: 10584

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14872 AN: 68000

Other (OTH) AF: 0.190 AC: 401 AN: 2116

Alfa AF: 0.203 Hom.: 14181

Bravo AF: 0.186

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		-0.82

Splicing

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

Other links and lift over

dbSNP: rs7236339; hg19: chr18-77579773;