7-150946906-G-C

Variant summary

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

The NM_000238.4(KCNH2):ā€‹c.3301C>Gā€‹(p.Pro1101Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

KCNH2
NM_000238.4 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92
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]

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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=0.30874753).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNH2NM_000238.4 linkuse as main transcriptc.3301C>G p.Pro1101Ala missense_variant 14/15 ENST00000262186.10 NP_000229.1 Q12809-1Q15BH2A0A090N8Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNH2ENST00000262186.10 linkuse as main transcriptc.3301C>G p.Pro1101Ala missense_variant 14/151 NM_000238.4 ENSP00000262186.5 Q12809-1
KCNH2ENST00000330883.9 linkuse as main transcriptc.2281C>G p.Pro761Ala missense_variant 10/111 ENSP00000328531.4 Q12809-2
KCNH2ENST00000684241.1 linkuse as main transcriptn.4134C>G non_coding_transcript_exon_variant 12/13

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1446848
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
717316
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:
9.07e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.40
.;T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.74
T;T
M_CAP
Pathogenic
0.38
D
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
0.69
.;N
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.8
N;N
REVEL
Uncertain
0.41
Sift
Benign
0.26
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.88
P;P
Vest4
0.34
MutPred
0.17
.;Loss of loop (P = 0.0128);
MVP
0.67
MPC
0.65
ClinPred
0.65
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.072
gMVP
0.24

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.

Other links and lift over

dbSNP: rs1347039291; hg19: chr7-150643994; API