7-150947431-C-G

Position:

• chr7-150947431-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000238.4(KCNH2):​c.3049G>C​(p.Ala1017Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
  • Exomes 𝑓: 0.000056 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNH2 NM_000238.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.229408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH2	NM_000238.4	c.3049G>C	p.Ala1017Pro	missense_variant	13/15	ENST00000262186.10	NP_000229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH2	ENST00000262186.10	c.3049G>C	p.Ala1017Pro	missense_variant	13/15	1	NM_000238.4	ENSP00000262186.5
KCNH2	ENST00000330883.9	c.2029G>C	p.Ala677Pro	missense_variant	9/11	1		ENSP00000328531.4
KCNH2	ENST00000684241.1	n.3882G>C		non_coding_transcript_exon_variant	11/13

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000564 AC: 73 AN: 1293224 Hom.: 0 Cov.: 35 AF XY: 0.0000499 AC XY: 32 AN XY: 641708

Gnomad4 AFR exome AF: 0.0000668

Gnomad4 AMR exome AF: 0.0000281

Gnomad4 ASJ exome AF: 0.0000416

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000389

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000618

Gnomad4 OTH exome AF: 0.0000923

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	0.34	.;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.50	N;N
REVEL	Uncertain	0.60
Sift	Benign	0.15	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.55	P;B
Vest4		0.25
MutPred		0.25		.;Gain of glycosylation at A1017 (P = 0.0014);
MVP		0.90
MPC		0.27
ClinPred		0.21	T
GERP RS		2.8
Varity_R		0.22
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr7-150644519;