Variant rs2072413 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000238.4(KCNH2):c.2145+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,599,804 control chromosomes in the GnomAD database, including 56,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6075 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50797 hom. )

Consequence

KCNH2
NM_000238.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.42

Variant links:

Genes affected

KCNH2 (HGNC:6251): (potassium voltage-gated channel subfamily H member 2) This gene encodes a component of a voltage-activated potassium channel found in cardiac muscle, nerve cells, and microglia. Four copies of this protein interact with one copy of the KCNE2 protein to form a functional potassium channel. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, May 2022]

KCNH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 7-150950881-C-T is Benign according to our data. Variant chr7-150950881-C-T is described in ClinVar as [Benign]. Clinvar id is 671018.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-150950881-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNH2	NM_000238.4 linkuse as main transcript	c.2145+40G>A		intron_variant		ENST00000262186.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH2	ENST00000262186.10 linkuse as main transcript	c.2145+40G>A		intron_variant		1	NM_000238.4	P1	Q12809-1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

41996

AN:

151884

Hom.:

6052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.275

GnomAD3 exomes

AF:

0.236

AC:

58838

AN:

249092

Hom.:

7194

AF XY:

0.240

AC XY:

32280

AN XY:

134660

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.261

AC:

377793

AN:

1447802

Hom.:

50797

Cov.:

AF XY:

0.261

AC XY:

187790

AN XY:

720862

show subpopulations

Gnomad4 AFR exome

AF:

0.354

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.272

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.277

AC:

42055

AN:

152002

Hom.:

6075

Cov.:

AF XY:

0.273

AC XY:

20283

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.270

Hom.:

1103

Bravo

AF:

0.277

Asia WGS

AF:

0.225

AC:

784

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

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

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