ENST00000715813.1:c.-2650-16483G>A

Variant names:

• chr21-34246337-G-A
• rs9978407
• ENST00000715813.1:c.-2650-16483G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000715813.1(KCNE2):​c.-2650-16483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,128 control chromosomes in the GnomAD database, including 1,476 homozygotes. 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: 𝑓 0.13 (1476 hom., cov: 32)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 11 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]

MRPS6 (HGNC:14051): (mitochondrial ribosomal protein S6) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S6P family. Pseudogenes corresponding to this gene are found on chromosomes 1p and 12q. [provided by RefSeq, Jul 2008]

LINC00310 (HGNC:16414): (long intergenic non-protein coding RNA 310)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE2	ENST00000715813.1	c.-2650-16483G>A		intron_variant	Intron 1 of 5			ENSP00000520524.1
MRPS6	ENST00000362077.5	n.227-16483G>A		intron_variant	Intron 3 of 6	3		ENSP00000520522.1
LINC00310	ENST00000427022.1	n.312-16483G>A		intron_variant	Intron 2 of 4	3
LINC00310	ENST00000715812.1	n.187-16483G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20372 AN: 152010 Hom.: 1477 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.134 AC: 20376 AN: 152128 Hom.: 1476 Cov.: 32 AF XY: 0.131 AC XY: 9706 AN XY: 74372

African (AFR) AF: 0.170 AC: 7046 AN: 41478

American (AMR) AF: 0.100 AC: 1529 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1391 AN: 10584

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9244 AN: 68000

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.141 Hom.: 546

Bravo AF: 0.133

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.40
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs9978407; hg19: chr21-35618638;