rs13048252

Variant names:

• chr21-34363867-G-A
• rs13048252
• ENST00000715813.1:c.-294G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-34363867-G-A
• chr21-34363867-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000715813.1(KCNE2):​c.-294G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,102 control chromosomes in the GnomAD database, including 22,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.52 (22151 hom., cov: 33)
• Consequence: KCNE2 ENST00000715813.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.09
• Publications: 4 publications found

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]

KCNE2 Gene-Disease associations (from GenCC):

• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• long QT syndrome 6

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000225555 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 21-34363867-G-A is Benign according to our data. Variant chr21-34363867-G-A is described in ClinVar as Benign. ClinVar VariationId is 683556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000715813.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC105372791	NR_188571.1		n.852+6568C>T		intron	N/A
	KCNE2	NM_172201.2	MANE Select	c.-297G>A		upstream_gene	N/A	NP_751951.1	Q9Y6J6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE2	ENST00000715813.1		c.-294G>A		5_prime_UTR	Exon 5 of 6	ENSP00000520524.1	Q9Y6J6
	ENSG00000225555	ENST00000440403.2	TSL:3	n.854+6568C>T		intron	N/A
	KCNE2	ENST00000290310.4	TSL:1 MANE Select	c.-297G>A		upstream_gene	N/A	ENSP00000290310.2	Q9Y6J6

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78332 AN: 151984 Hom.: 22155 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.515 AC: 78334 AN: 152102 Hom.: 22151 Cov.: 33 AF XY: 0.523 AC XY: 38872 AN XY: 74344

African (AFR) AF: 0.273 AC: 11306 AN: 41482

American (AMR) AF: 0.598 AC: 9142 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1975 AN: 3468

East Asian (EAS) AF: 0.758 AC: 3918 AN: 5170

South Asian (SAS) AF: 0.583 AC: 2805 AN: 4814

European-Finnish (FIN) AF: 0.631 AC: 6673 AN: 10568

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40626 AN: 67998

Other (OTH) AF: 0.542 AC: 1144 AN: 2110

Alfa AF: 0.579 Hom.: 110832

Bravo AF: 0.506

Asia WGS AF: 0.634 AC: 2209 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		1.1
PromoterAI		-0.023	Neutral

Splicing

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

Other links and lift over

dbSNP: rs13048252; hg19: chr21-35736166;