7-150946905-G-C

Variant summary

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

The NM_000238.4(KCNH2):c.3302C>G(p.Pro1101Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P1101L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: KCNH2 NM_000238.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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/exons	MANE	UniProt
KCNH2	NM_000238.4	c.3302C>G	p.Pro1101Arg	missense_variant	14/15	ENST00000262186.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH2	ENST00000262186.10	c.3302C>G	p.Pro1101Arg	missense_variant	14/15	1	NM_000238.4	P1
KCNH2	ENST00000330883.9	c.2282C>G	p.Pro761Arg	missense_variant	10/11	1
KCNH2	ENST00000684241.1	n.4135C>G		non_coding_transcript_exon_variant	12/13

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74468

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
CardioboostArm	Benign	0.0014
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Pathogenic	0.82	D
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.54
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.055	T;T
Polyphen		0.96	D;P
Vest4		0.33
MutPred		0.17		.;Loss of glycosylation at T1102 (P = 0.0278);
MVP		0.82
MPC		0.71
ClinPred		0.70	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.12
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150643993;