rs1555837113

chr21-34370763-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_172201.2(KCNE2):c.285G>T(p.Lys95Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNE2 NM_172201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNE2	NM_172201.2	c.285G>T	p.Lys95Asn	missense_variant	2/2	ENST00000290310.4
LOC105372791	XR_937683.3	n.1091C>A		non_coding_transcript_exon_variant	2/2
LOC105372791	XR_007067848.1	n.1126C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE2	ENST00000290310.4	c.285G>T	p.Lys95Asn	missense_variant	2/2	1	NM_172201.2	P1
	ENST00000440403.2	n.526C>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary dilated cardiomyopathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Human Genetics, University of Leuven

Apr 30, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.92	D
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	0.84	D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.085	T
Polyphen		0.51	P
Vest4		0.39
MutPred		0.55		Loss of methylation at K95 (P = 0.0087);
MVP		0.92
MPC		0.29
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.34
gMVP		0.72

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: rs1555837113; hg19: chr21-35743062;