rs2269001

Positions:

• chr7-150954728-G-A
• chr7-150954728-G-C
• chr7-150954728-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000238.4(KCNH2):​c.1129-1875C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,074 control chromosomes in the GnomAD database, including 6,218 homozygotes. 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: 𝑓 0.27 (6218 hom., cov: 33)
• Consequence: KCNH2 NM_000238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNH2	NM_000238.4	c.1129-1875C>T		intron_variant		ENST00000262186.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH2	ENST00000262186.10	c.1129-1875C>T		intron_variant		1	NM_000238.4	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41135 AN: 151956 Hom.: 6200 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.264

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 41187 AN: 152074 Hom.: 6218 Cov.: 33 AF XY: 0.279 AC XY: 20725 AN XY: 74318

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.271

Alfa AF: 0.239 Hom.: 650

Bravo AF: 0.278

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2269001; hg19: chr7-150651816;