21-34308001-T-C

Variant names:

• chr21-34308001-T-C
• rs4817639
• ENST00000715813.1:c.-2473+14245T>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+14245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,162 control chromosomes in the GnomAD database, including 50,948 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 0.82 (50948 hom., cov: 32)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 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+14245T>C		intron_variant	Intron 3 of 5			ENSP00000520524.1
MRPS6	ENST00000362077.5	n.*155+14245T>C		intron_variant	Intron 5 of 6	3		ENSP00000520522.1
LINC00310	ENST00000427022.1	n.506+14245T>C		intron_variant	Intron 4 of 4	3
LINC00310	ENST00000715812.1	n.364+14245T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124169 AN: 152044 Hom.: 50900 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.817 AC: 124278 AN: 152162 Hom.: 50948 Cov.: 32 AF XY: 0.823 AC XY: 61188 AN XY: 74388

African (AFR) AF: 0.824 AC: 34188 AN: 41510

American (AMR) AF: 0.844 AC: 12910 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2797 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5158 AN: 5178

South Asian (SAS) AF: 0.892 AC: 4291 AN: 4808

European-Finnish (FIN) AF: 0.838 AC: 8870 AN: 10590

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53352 AN: 67992

Other (OTH) AF: 0.809 AC: 1708 AN: 2110

Alfa AF: 0.797 Hom.: 61137

Bravo AF: 0.816

Asia WGS AF: 0.942 AC: 3275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.56
PhyloP100		-1.9

Splicing

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

Publications

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Other links and lift over

dbSNP: rs4817639; hg19: chr21-35680301;