rs9984281

chr21-34369557-A-Gchr21-34369557-A-T

Variant summary

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

The NM_172201.2(KCNE2):c.-12-910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,060 control chromosomes in the GnomAD database, including 2,382 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 0.17 (2382 hom., cov: 32)
• Consequence: KCNE2 NM_172201.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

KCNE2 (HGNC:6242): (potassium voltage-gated channel subfamily E regulatory subunit 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, isk-related subfamily. This member is a small integral membrane subunit that assembles with the KCNH2 gene product, a pore-forming protein, to alter its function. This gene is expressed in heart and muscle and the gene mutations are associated with cardiac arrhythmia. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNE2	NM_172201.2	c.-12-910A>G		intron_variant		ENST00000290310.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE2	ENST00000290310.4	c.-12-910A>G		intron_variant		1	NM_172201.2	P1
	ENST00000440403.2	n.854+878T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25754 AN: 151942 Hom.: 2376 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.0999

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.170 AC: 25785 AN: 152060 Hom.: 2382 Cov.: 32 AF XY: 0.169 AC XY: 12597 AN XY: 74330

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.0999

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.167

Alfa AF: 0.167 Hom.: 995

Bravo AF: 0.170

Asia WGS AF: 0.219 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.22
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9984281; hg19: chr21-35741856;