rs41307289

Positions:

• chr7-150949840-G-A
• chr7-150949840-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172056.3(KCNH2):​c.*59C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,271,754 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (18 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (154 hom.)
• Consequence: KCNH2 NM_172056.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.79

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]

KCNH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-150949840-G-A is Benign according to our data. Variant chr7-150949840-G-A is described in ClinVar as [Benign]. Clinvar id is 1290932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH2	NM_000238.4	c.2398+328C>T		intron_variant		ENST00000262186.10	NP_000229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH2	ENST00000262186.10	c.2398+328C>T		intron_variant		1	NM_000238.4	ENSP00000262186.5

Frequencies

GnomAD3 genomes AF: 0.00549 AC: 836 AN: 152166 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00461 AC: 5156 AN: 1119470 Hom.: 154 Cov.: 30 AF XY: 0.00590 AC XY: 3180 AN XY: 539036

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.0150

Gnomad4 ASJ exome AF: 0.000315

Gnomad4 EAS exome AF: 0.0863

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.00312

Gnomad4 NFE exome AF: 0.000273

Gnomad4 OTH exome AF: 0.00654

GnomAD4 genome AF: 0.00547 AC: 833 AN: 152284 Hom.: 18 Cov.: 31 AF XY: 0.00673 AC XY: 501 AN XY: 74470

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00699

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0810

Gnomad4 SAS AF: 0.0437

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00138 Hom.: 1

Bravo AF: 0.00523

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.41

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: rs41307289; hg19: chr7-150646928;