rs1013063

Variant names:

• chr21-34326090-T-C
• rs1013063
• ENST00000715813.1:c.-2473+32334T>C

Variant summary

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

The ENST00000715813.1(KCNE2):​c.-2473+32334T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,890 control chromosomes in the GnomAD database, including 19,686 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 0.49 (19686 hom., cov: 31)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.616 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.-2473+32334T>C		intron_variant	Intron 3 of 5			ENSP00000520524.1
MRPS6	ENST00000362077.5	n.*155+32334T>C		intron_variant	Intron 5 of 6	3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74561 AN: 151772 Hom.: 19687 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.491 AC: 74572 AN: 151890 Hom.: 19686 Cov.: 31 AF XY: 0.499 AC XY: 37047 AN XY: 74228

African (AFR) AF: 0.290 AC: 12026 AN: 41406

American (AMR) AF: 0.627 AC: 9574 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2241 AN: 5140

South Asian (SAS) AF: 0.541 AC: 2601 AN: 4808

European-Finnish (FIN) AF: 0.640 AC: 6731 AN: 10520

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.562 AC: 38200 AN: 67966

Other (OTH) AF: 0.486 AC: 1024 AN: 2106

Alfa AF: 0.486 Hom.: 9782

Bravo AF: 0.481

Asia WGS AF: 0.454 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.52
PhyloP100		0.040

Splicing

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

Other links and lift over

dbSNP: rs1013063; hg19: chr21-35698390;