rs41260744

Variant names:

• chr21-34364085-G-A
• rs41260744
• NM_172201.2:c.-79G>A

Variant summary

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

The NM_172201.2(KCNE2):​c.-79G>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 0.0783 in 152,298 control chromosomes in the GnomAD database, including 568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (567 hom., cov: 33)
  • Exomes 𝑓: 0.077 (1 hom.)
• Consequence: KCNE2 NM_172201.2 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.18
• Publications: 6 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=-0.92).
• BP6: Variant 21-34364085-G-A is Benign according to our data. Variant chr21-34364085-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 339716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172201.2. 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
	KCNE2	NM_172201.2	MANE Select	c.-79G>A		5_prime_UTR	Exon 1 of 2	NP_751951.1	Q9Y6J6
	LOC105372791	NR_188571.1		n.852+6350C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE2	ENST00000290310.4	TSL:1 MANE Select	c.-79G>A		5_prime_UTR	Exon 1 of 2	ENSP00000290310.2	Q9Y6J6
	KCNE2	ENST00000715813.1		c.-76G>A		5_prime_UTR	Exon 5 of 6	ENSP00000520524.1	Q9Y6J6
	ENSG00000225555	ENST00000440403.2	TSL:3	n.854+6350C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11904 AN: 152128 Hom.: 560 Cov.: 33

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.0867

GnomAD4 exome AF: 0.0769 AC: 4 AN: 52 Hom.: 1 Cov.: 0 AF XY: 0.0500 AC XY: 2 AN XY: 40

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0227 AC: 1 AN: 44

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.0783 AC: 11928 AN: 152246 Hom.: 567 Cov.: 33 AF XY: 0.0799 AC XY: 5948 AN XY: 74450

African (AFR) AF: 0.0781 AC: 3246 AN: 41568

American (AMR) AF: 0.0895 AC: 1367 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3472

East Asian (EAS) AF: 0.179 AC: 926 AN: 5180

South Asian (SAS) AF: 0.114 AC: 548 AN: 4826

European-Finnish (FIN) AF: 0.0624 AC: 662 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0656 AC: 4459 AN: 68002

Other (OTH) AF: 0.0900 AC: 190 AN: 2110

Alfa AF: 0.0710 Hom.: 105

Bravo AF: 0.0786

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Atrial fibrillation, familial, 4 (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.010
DANN	Benign	0.52
PhyloP100		-1.2
Mutation Taster		=300/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41260744;

hg19: chr21-35736384;