21-34199605-G-A

Variant names:

• chr21-34199605-G-A
• rs8131349
• ENST00000715813.1:c.-2651+18812G>A

Variant summary

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

The ENST00000715813.1(KCNE2):​c.-2651+18812G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 151,244 control chromosomes in the GnomAD database, including 332 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 0.052 (332 hom., cov: 30)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 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.-2651+18812G>A		intron	N/A	ENSP00000520524.1
	MRPS6	ENST00000362077.5	TSL:3	n.186-15895G>A		intron	N/A	ENSP00000520522.1
	LINC00310	ENST00000715812.1		n.186+18812G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7926 AN: 151132 Hom.: 329 Cov.: 30

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0912

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0559

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

GnomAD4 genome AF: 0.0525 AC: 7939 AN: 151244 Hom.: 332 Cov.: 30 AF XY: 0.0550 AC XY: 4063 AN XY: 73812

African (AFR) AF: 0.0160 AC: 660 AN: 41196

American (AMR) AF: 0.0383 AC: 582 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 316 AN: 3464

East Asian (EAS) AF: 0.188 AC: 962 AN: 5122

South Asian (SAS) AF: 0.155 AC: 738 AN: 4752

European-Finnish (FIN) AF: 0.0893 AC: 928 AN: 10388

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0525 AC: 3563 AN: 67818

Other (OTH) AF: 0.0578 AC: 121 AN: 2094

Alfa AF: 0.0480 Hom.: 239

Bravo AF: 0.0465

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.38
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs8131349; hg19: chr21-35571906;