21-34370423-C-T

Variant names:

• chr21-34370423-C-T
• rs9305548
• NM_172201.2:c.-12-44C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172201.2(KCNE2):​c.-12-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,612,532 control chromosomes in the GnomAD database, including 29,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6030 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23704 hom.)
• Consequence: KCNE2 NM_172201.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134

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]

ENSG00000225555 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 21-34370423-C-T is Benign according to our data. Variant chr21-34370423-C-T is described in ClinVar as [Benign]. Clinvar id is 1242701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE2	NM_172201.2	c.-12-44C>T		intron_variant	Intron 1 of 1	ENST00000290310.4	NP_751951.1
LOC105372791	NR_188572.1	n.864G>A		non_coding_transcript_exon_variant	Exon 2 of 2
LOC105372791	NR_188571.1	n.852+12G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE2	ENST00000290310.4	c.-12-44C>T		intron_variant	Intron 1 of 1	1	NM_172201.2	ENSP00000290310.2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36782 AN: 151978 Hom.: 5998 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.168 AC: 244884 AN: 1460436 Hom.: 23704 Cov.: 31 AF XY: 0.171 AC XY: 124123 AN XY: 726638

African (AFR) AF: 0.476 AC: 15923 AN: 33432

American (AMR) AF: 0.139 AC: 6213 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 5259 AN: 26128

East Asian (EAS) AF: 0.246 AC: 9768 AN: 39694

South Asian (SAS) AF: 0.295 AC: 25412 AN: 86064

European-Finnish (FIN) AF: 0.104 AC: 5538 AN: 53386

Middle Eastern (MID) AF: 0.198 AC: 1141 AN: 5764

European-Non Finnish (NFE) AF: 0.148 AC: 164324 AN: 1110910

Other (OTH) AF: 0.187 AC: 11306 AN: 60342

GnomAD4 genome AF: 0.242 AC: 36873 AN: 152096 Hom.: 6030 Cov.: 32 AF XY: 0.239 AC XY: 17772 AN XY: 74356

African (AFR) AF: 0.458 AC: 18996 AN: 41468

American (AMR) AF: 0.185 AC: 2823 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 709 AN: 3464

East Asian (EAS) AF: 0.226 AC: 1169 AN: 5184

South Asian (SAS) AF: 0.295 AC: 1425 AN: 4826

European-Finnish (FIN) AF: 0.0995 AC: 1054 AN: 10592

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10008 AN: 67972

Other (OTH) AF: 0.217 AC: 458 AN: 2112

Alfa AF: 0.203 Hom.: 6475

Bravo AF: 0.253

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.97
DANN	Benign	0.54
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: rs9305548; hg19: chr21-35742722; COSMIC: COSV51711052; COSMIC: COSV51711052;