Variant 21-34370451-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_172201.2(KCNE2):c.-12-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,614,000 control chromosomes in the GnomAD database, including 2,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 777 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1477 hom. )

Consequence

KCNE2
NM_172201.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.146

Variant links:

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]

KCNE2 links:

ENSG00000225555 (HGNC:):

ENSG00000225555 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 21-34370451-A-G is Benign according to our data. Variant chr21-34370451-A-G is described in ClinVar as [Benign]. Clinvar id is 262799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-34370451-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
KCNE2	NM_172201.2 linkuse as main transcript	c.-12-16A>G	intron_variant		ENST00000290310.4	NP_751951.1	Q9Y6J6
LOC105372791	NR_188571.1 linkuse as main transcript	n.836T>C	non_coding_transcript_exon_variant	2/3
LOC105372791	NR_188572.1 linkuse as main transcript	n.836T>C	non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE2	ENST00000290310.4 linkuse as main transcript	c.-12-16A>G		intron_variant		1	NM_172201.2	ENSP00000290310.2		Q9Y6J6
ENSG00000225555	ENST00000440403.2 linkuse as main transcript	n.838T>C		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0730

AC:

11101

AN:

152148

Hom.:

768

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0387

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0626

GnomAD3 exomes

AF:

0.0365

AC:

9133

AN:

250390

Hom.:

403

AF XY:

0.0349

AC XY:

4739

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0206

Gnomad ASJ exome

AF:

0.0281

Gnomad EAS exome

AF:

0.000924

Gnomad SAS exome

AF:

0.0391

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0295

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0361

AC:

52789

AN:

1461734

Hom.:

1477

Cov.:

AF XY:

0.0360

AC XY:

26171

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.0238

Gnomad4 ASJ exome

AF:

0.0285

Gnomad4 EAS exome

AF:

0.00207

Gnomad4 SAS exome

AF:

0.0398

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0336

Gnomad4 OTH exome

AF:

0.0436

GnomAD4 genome

AF:

0.0731

AC:

11132

AN:

152266

Hom.:

777

Cov.:

AF XY:

0.0698

AC XY:

5200

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.0396

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0390

Gnomad4 FIN

AF:

0.0138

Gnomad4 NFE

AF:

0.0325

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0472

Hom.:

Bravo

AF:

0.0796

Asia WGS

AF:

0.0380

AC:

130

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.0

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over