7-150947801-C-G

Variant names:

• chr7-150947801-C-G
• rs794728397
• NM_000238.4:c.2770G>C

Variant summary

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

The NM_000238.4(KCNH2):​c.2770G>C​(p.Gly924Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,378,468 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: KCNH2 NM_000238.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH2	NM_000238.4	c.2770G>C	p.Gly924Arg	missense_variant	Exon 12 of 15	ENST00000262186.10	NP_000229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH2	ENST00000262186.10	c.2770G>C	p.Gly924Arg	missense_variant	Exon 12 of 15	1	NM_000238.4	ENSP00000262186.5
KCNH2	ENST00000330883.9	c.1750G>C	p.Gly584Arg	missense_variant	Exon 8 of 11	1		ENSP00000328531.4
KCNH2	ENST00000684241.1	n.3603G>C		non_coding_transcript_exon_variant	Exon 10 of 13

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1378468 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 679460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000283

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: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.097
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.82	T;T
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Benign	0.55	.;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.64	N;N
REVEL	Uncertain	0.55
Sift	Benign	0.27	T;T
Sift4G	Benign	0.68	T;T
Polyphen		1.0	D;D
Vest4		0.39
MutPred		0.44		.;Gain of MoRF binding (P = 0.0183);
MVP		0.97
MPC		0.23
ClinPred		0.62	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.55

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

Other links and lift over

dbSNP: rs794728397; hg19: chr7-150644889;