ENST00000715813.1:c.-2548-13742A>T

Variant names:

• chr21-34279939-A-T
• rs9978142
• ENST00000715813.1:c.-2548-13742A>T

Variant summary

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

The ENST00000715813.1(KCNE2):​c.-2548-13742A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,170 control chromosomes in the GnomAD database, including 1,850 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 0.15 (1850 hom., cov: 32)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 33 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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.-2548-13742A>T		intron_variant	Intron 2 of 5			ENSP00000520524.1
MRPS6	ENST00000362077.5	n.*80-13742A>T		intron_variant	Intron 4 of 6	3		ENSP00000520522.1
LINC00310	ENST00000427022.1	n.431-13742A>T		intron_variant	Intron 3 of 4	3
LINC00310	ENST00000715812.1	n.289-13742A>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22853 AN: 152052 Hom.: 1851 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0659

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.150 AC: 22863 AN: 152170 Hom.: 1850 Cov.: 32 AF XY: 0.146 AC XY: 10828 AN XY: 74386

African (AFR) AF: 0.194 AC: 8044 AN: 41508

American (AMR) AF: 0.107 AC: 1631 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0662 AC: 319 AN: 4820

European-Finnish (FIN) AF: 0.139 AC: 1472 AN: 10578

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10440 AN: 68002

Other (OTH) AF: 0.140 AC: 295 AN: 2112

Alfa AF: 0.146 Hom.: 953

Bravo AF: 0.149

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.43
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs9978142; hg19: chr21-35652239;