rs7526730

Positions:

• chr1-110523131-C-T

Variant summary

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

The ENST00000640680.1(KCNA2):​n.2732-833G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,226 control chromosomes in the GnomAD database, including 1,386 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 0.13 (1386 hom., cov: 32)
• Consequence: KCNA2 ENST00000640680.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

Genes affected

KCNA2 (HGNC:6220): (potassium voltage-gated channel subfamily A member 2) Potassium 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNA2	ENST00000640680.1	n.2732-833G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20056 AN: 152108 Hom.: 1381 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.132 AC: 20092 AN: 152226 Hom.: 1386 Cov.: 32 AF XY: 0.132 AC XY: 9795 AN XY: 74408

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0479

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.135

Alfa AF: 0.138 Hom.: 1964

Bravo AF: 0.131

Asia WGS AF: 0.133 AC: 465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7526730; hg19: chr1-111065753;