rs8128316

Variant names:

• chr21-34349261-C-T
• rs8128316
• ENST00000715813.1:c.-2472-10645C>T

Variant summary

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

The ENST00000715813.1(KCNE2):​c.-2472-10645C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,794 control chromosomes in the GnomAD database, including 22,567 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 0.54 (22567 hom., cov: 31)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000715813.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE2	ENST00000715813.1		c.-2472-10645C>T		intron	N/A	ENSP00000520524.1
	MRPS6	ENST00000362077.5	TSL:3	n.*156-10645C>T		intron	N/A	ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81573 AN: 151676 Hom.: 22535 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.538 AC: 81655 AN: 151794 Hom.: 22567 Cov.: 31 AF XY: 0.542 AC XY: 40171 AN XY: 74170

African (AFR) AF: 0.626 AC: 25911 AN: 41370

American (AMR) AF: 0.612 AC: 9346 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3466

East Asian (EAS) AF: 0.445 AC: 2289 AN: 5144

South Asian (SAS) AF: 0.427 AC: 2056 AN: 4810

European-Finnish (FIN) AF: 0.593 AC: 6236 AN: 10520

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32910 AN: 67918

Other (OTH) AF: 0.503 AC: 1059 AN: 2106

Alfa AF: 0.499 Hom.: 36660

Bravo AF: 0.546

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs8128316; hg19: chr21-35721560;