rs9305548

Positions:

• chr21-34370423-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172201.2(KCNE2):​c.-12-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,612,532 control chromosomes in the GnomAD database, including 29,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6030 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23704 hom.)
• Consequence: KCNE2 NM_172201.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 21-34370423-C-T is Benign according to our data. Variant chr21-34370423-C-T is described in ClinVar as [Benign]. Clinvar id is 1242701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE2	NM_172201.2	c.-12-44C>T		intron_variant		ENST00000290310.4	NP_751951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE2	ENST00000290310.4	c.-12-44C>T		intron_variant		1	NM_172201.2	ENSP00000290310	P1
	ENST00000440403.2	n.854+12G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36782 AN: 151978 Hom.: 5998 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.168 AC: 244884 AN: 1460436 Hom.: 23704 Cov.: 31 AF XY: 0.171 AC XY: 124123 AN XY: 726638

Gnomad4 AFR exome AF: 0.476

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.242 AC: 36873 AN: 152096 Hom.: 6030 Cov.: 32 AF XY: 0.239 AC XY: 17772 AN XY: 74356

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.0995

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.217

Alfa AF: 0.172 Hom.: 2734

Bravo AF: 0.253

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.97
DANN	Benign	0.54

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: rs9305548; hg19: chr21-35742722; COSMIC: COSV51711052; COSMIC: COSV51711052;