rs2834462

Variant names:

• chr21-34344892-T-C
• rs2834462
• ENST00000715813.1:c.-2472-15014T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-34344892-T-C
• chr21-34344892-T-G

Variant summary

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

The ENST00000715813.1(KCNE2):​c.-2472-15014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,986 control chromosomes in the GnomAD database, including 38,420 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 0.71 (38420 hom., cov: 31)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 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.-2472-15014T>C		intron_variant	Intron 3 of 5			ENSP00000520524.1
MRPS6	ENST00000362077.5	n.*156-15014T>C		intron_variant	Intron 5 of 6	3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107261 AN: 151868 Hom.: 38379 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.706 AC: 107358 AN: 151986 Hom.: 38420 Cov.: 31 AF XY: 0.707 AC XY: 52548 AN XY: 74282

African (AFR) AF: 0.798 AC: 33074 AN: 41460

American (AMR) AF: 0.751 AC: 11478 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2256 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2476 AN: 5150

South Asian (SAS) AF: 0.685 AC: 3300 AN: 4816

European-Finnish (FIN) AF: 0.702 AC: 7405 AN: 10550

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45032 AN: 67942

Other (OTH) AF: 0.690 AC: 1457 AN: 2112

Alfa AF: 0.686 Hom.: 28476

Bravo AF: 0.711

Asia WGS AF: 0.596 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.031
DANN	Benign	0.35
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs2834462; hg19: chr21-35717191;