Variant 7-150947729-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000238.4(KCNH2):c.2842C>A(p.Arg948Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,412,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KCNH2
NM_000238.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 3.14

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37753955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH2	NM_000238.4 link	c.2842C>A	p.Arg948Ser	missense_variant	12/15	ENST00000262186.10	NP_000229.1	Q12809-1Q15BH2A0A090N8Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNH2	ENST00000262186.10 link	c.2842C>A	p.Arg948Ser	missense_variant	12/15	1	NM_000238.4	ENSP00000262186.5	Q12809-1
KCNH2	ENST00000330883.9 link	c.1822C>A	p.Arg608Ser	missense_variant	8/11	1		ENSP00000328531.4	Q12809-2
KCNH2	ENST00000684241.1 link	n.3675C>A		non_coding_transcript_exon_variant	10/13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000602

AC:

AN:

166182

Hom.:

AF XY:

0.00

AC XY:

AN XY:

91106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000147

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1412928

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

699314

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

Congenital long QT syndrome

Other:1

not provided, no classification provided

literature only

Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust

This variant has been reported as associated with Long QT syndrome in the following publications (PMID:20541041). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.72

T;T

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.38

T;T

MetaSVM

Uncertain

0.34

MutationAssessor

Benign

0.0

.;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.43

N;N

REVEL

Uncertain

0.53

Sift

Benign

0.73

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.0

B;B

Vest4

0.51

MutPred

0.40

.;Gain of phosphorylation at R948 (P = 0.0012);

MVP

0.99

MPC

0.20

ClinPred

0.34

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.30

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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