7-150977888-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000238.4(KCNH2):​c.26C>A​(p.Ala9Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,856 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.

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KCNH2
NM_000238.4 missense

Scores

10
8
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.29
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNH2NM_000238.4 linkc.26C>A p.Ala9Glu missense_variant Exon 1 of 15 ENST00000262186.10 NP_000229.1 Q12809-1Q15BH2A0A090N8Q0
KCNH2NM_172056.3 linkc.26C>A p.Ala9Glu missense_variant Exon 1 of 9 NP_742053.1 Q12809-5A0A090N7W1Q15BH2
KCNH2NR_176254.1 linkn.434C>A non_coding_transcript_exon_variant Exon 1 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNH2ENST00000262186.10 linkc.26C>A p.Ala9Glu missense_variant Exon 1 of 15 1 NM_000238.4 ENSP00000262186.5 Q12809-1
KCNH2ENST00000532957.5 linkn.249C>A non_coding_transcript_exon_variant Exon 1 of 9 2

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455856
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
724150
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.71
D
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Pathogenic
1.0
D
M_CAP
Pathogenic
1.0
D
MetaRNN
Pathogenic
0.77
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Pathogenic
0.92
D
PROVEAN
Uncertain
-2.8
D
REVEL
Pathogenic
0.79
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.65
P
Vest4
0.49
MutPred
0.57
Gain of disorder (P = 0.0349);
MVP
0.85
MPC
1.9
ClinPred
0.95
D
GERP RS
2.5
Varity_R
0.49
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150674976; API