rs74424227

Positions:

• chr21-34370759-A-T
• chr21-34370759-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172201.2(KCNE2):​c.281A>T​(p.Glu94Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: KCNE2 NM_172201.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22204214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE2	NM_172201.2	c.281A>T	p.Glu94Val	missense_variant	2/2	ENST00000290310.4	NP_751951.1
LOC105372791	XR_937683.3	n.1095T>A		non_coding_transcript_exon_variant	2/2
LOC105372791	XR_007067848.1	n.1130T>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE2	ENST00000290310.4	c.281A>T	p.Glu94Val	missense_variant	2/2	1	NM_172201.2	ENSP00000290310	P1
	ENST00000440403.2	n.530T>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.84	D
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	-0.046	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.040	D
Polyphen		0.0030	B
Vest4		0.27
MutPred		0.42		Loss of disorder (P = 0.0499);
MVP		0.79
MPC		0.13
ClinPred		0.63	D
GERP RS		2.0
Varity_R		0.47
gMVP		0.66

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: rs74424227; hg19: chr21-35743058;