7-150947306-C-T

Position:

• chr7-150947306-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000238.4(KCNH2):​c.3152+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,529,804 control chromosomes in the GnomAD database, including 56,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.29 (7042 hom., cov: 32)
  • Exomes 𝑓: 0.25 (49747 hom.)
• Consequence: KCNH2 NM_000238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-150947306-C-T is Benign according to our data. Variant chr7-150947306-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNH2	NM_000238.4	c.3152+22G>A		intron_variant		ENST00000262186.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH2	ENST00000262186.10	c.3152+22G>A		intron_variant		1	NM_000238.4	P1
KCNH2	ENST00000330883.9	c.2132+22G>A		intron_variant		1
KCNH2	ENST00000684241.1	n.3985+22G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43423 AN: 151842 Hom.: 7026 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.278

GnomAD3 exomes AF: 0.335 AC: 45290 AN: 135222 Hom.: 9041 AF XY: 0.331 AC XY: 24266 AN XY: 73416

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.416

Gnomad ASJ exome AF: 0.338

Gnomad EAS exome AF: 0.708

Gnomad SAS exome AF: 0.361

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.248 AC: 341706 AN: 1377844 Hom.: 49747 Cov.: 32 AF XY: 0.252 AC XY: 171253 AN XY: 679968

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.754

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.286 AC: 43467 AN: 151960 Hom.: 7042 Cov.: 32 AF XY: 0.295 AC XY: 21883 AN XY: 74280

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.285

Alfa AF: 0.177 Hom.: 561

Bravo AF: 0.294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.90

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: rs3815459; hg19: chr7-150644394; COSMIC: COSV51211598; COSMIC: COSV51211598;