Variant 7-150948477-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM5PP3BS2

The NM_000238.4(KCNH2):c.2659C>A(p.Arg887Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000891 in 1,459,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R887H) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

KCNH2
NM_000238.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98

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:

KCNH2 (HGNC:):

KCNH2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr7-150948476-C-T is described in Lovd as [Pathogenic].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.768

BS2

High AC in GnomAdExome4 at 13 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH2	NM_000238.4 linkuse as main transcript	c.2659C>A	p.Arg887Ser	missense_variant	11/15	ENST00000262186.10	NP_000229.1	Q12809-1Q15BH2A0A090N8Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNH2	ENST00000262186.10 linkuse as main transcript	c.2659C>A	p.Arg887Ser	missense_variant	11/15	1	NM_000238.4	ENSP00000262186.5	Q12809-1
KCNH2	ENST00000330883.9 linkuse as main transcript	c.1639C>A	p.Arg547Ser	missense_variant	7/11	1		ENSP00000328531.4	Q12809-2
KCNH2	ENST00000684241.1 linkuse as main transcript	n.3492C>A		non_coding_transcript_exon_variant	9/13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249022

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134942

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:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459630

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726252

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

.;D

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.83

T;T

M_CAP

Pathogenic

0.90

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

1.8

.;L

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.4

N;N

REVEL

Pathogenic

0.81

Sift

Benign

0.045

D;D

Sift4G

Benign

0.23

T;T

Polyphen

0.97

D;P

Vest4

0.53

MutPred

0.41

.;Gain of phosphorylation at R887 (P = 0.0085);

MVP

0.97

MPC

0.64

ClinPred

0.82

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.88

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over