rs2834442

Variant names:

• chr21-34318486-T-A
• rs2834442
• ENST00000715813.1:c.-2473+24730T>A

Your query was ambiguous. Multiple possible variants found:

• chr21-34318486-T-A
• chr21-34318486-T-C
• chr21-34318486-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000362077.5(MRPS6):​n.*155+24730T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,084 control chromosomes in the GnomAD database, including 32,479 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 0.65 (32479 hom., cov: 32)
• Consequence: MRPS6 ENST00000362077.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 44 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000362077.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE2	ENST00000715813.1		c.-2473+24730T>A		intron	N/A	ENSP00000520524.1
	MRPS6	ENST00000362077.5	TSL:3	n.*155+24730T>A		intron	N/A	ENSP00000520522.1
	LINC00310	ENST00000427022.1	TSL:3	n.507-6250T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98963 AN: 151966 Hom.: 32458 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.651 AC: 99039 AN: 152084 Hom.: 32479 Cov.: 32 AF XY: 0.656 AC XY: 48778 AN XY: 74336

African (AFR) AF: 0.618 AC: 25612 AN: 41460

American (AMR) AF: 0.717 AC: 10962 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2618 AN: 5174

South Asian (SAS) AF: 0.708 AC: 3412 AN: 4822

European-Finnish (FIN) AF: 0.700 AC: 7405 AN: 10578

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44546 AN: 67980

Other (OTH) AF: 0.649 AC: 1368 AN: 2108

Alfa AF: 0.649 Hom.: 17805

Bravo AF: 0.648

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs2834442; hg19: chr21-35690786;