rs3800779

chr7-150974126-C-Achr7-150974126-C-T

Variant summary

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

The NM_000238.4(KCNH2):c.307+585G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,012 control chromosomes in the GnomAD database, including 5,883 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 0.26 (5883 hom., cov: 33)
• Consequence: KCNH2 NM_000238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNH2	NM_000238.4	c.307+585G>T		intron_variant		ENST00000262186.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH2	ENST00000262186.10	c.307+585G>T		intron_variant		1	NM_000238.4	P1
KCNH2	ENST00000532957.5	n.530+585G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39925 AN: 151894 Hom.: 5888 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.263 AC: 39923 AN: 152012 Hom.: 5883 Cov.: 33 AF XY: 0.259 AC XY: 19264 AN XY: 74294

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.265

Alfa AF: 0.244 Hom.: 986

Bravo AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.9
Dann	Benign	0.75

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: rs3800779; hg19: chr7-150671214; COSMIC: COSV51131278;