chr21-34356981-A-G

Variant names:

• chr21-34356981-A-G
• rs2834467
• ENST00000715813.1:c.-2472-2925A>G

Variant summary

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

The ENST00000715813.1(KCNE2):​c.-2472-2925A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,750 control chromosomes in the GnomAD database, including 33,558 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 0.64 (33558 hom., cov: 29)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 5 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]

ENSG00000225555 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 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
	LOC105372791	NR_188571.1		n.853-2094T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE2	ENST00000715813.1		c.-2472-2925A>G		intron	N/A	ENSP00000520524.1
	MRPS6	ENST00000362077.5	TSL:3	n.*156-2925A>G		intron	N/A	ENSP00000520522.1
	ENSG00000225555	ENST00000440403.2	TSL:3	n.855-2094T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97646 AN: 151632 Hom.: 33562 Cov.: 29

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.644 AC: 97662 AN: 151750 Hom.: 33558 Cov.: 29 AF XY: 0.650 AC XY: 48183 AN XY: 74150

African (AFR) AF: 0.380 AC: 15714 AN: 41364

American (AMR) AF: 0.744 AC: 11328 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2437 AN: 3468

East Asian (EAS) AF: 0.794 AC: 4098 AN: 5164

South Asian (SAS) AF: 0.696 AC: 3347 AN: 4808

European-Finnish (FIN) AF: 0.772 AC: 8106 AN: 10504

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50318 AN: 67898

Other (OTH) AF: 0.677 AC: 1429 AN: 2112

Alfa AF: 0.693 Hom.: 19844

Bravo AF: 0.634

Asia WGS AF: 0.741 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.47
DANN	Benign	0.73
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs2834467; hg19: chr21-35729280;