2-162384337-T-G

Position:

• chr2-162384337-T-G

Variant summary

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

The NM_033272.4(KCNH7):​c.2962+351A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,620 control chromosomes in the GnomAD database, including 16,677 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 0.43 (16677 hom., cov: 31)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

Genes affected

KCNH7 (HGNC:18863): (potassium voltage-gated channel subfamily H member 7) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit. There are at least two alternatively spliced transcript variants derived from this gene and encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.2962+351A>C		intron_variant		ENST00000332142.10	NP_150375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10	c.2962+351A>C		intron_variant		1	NM_033272.4	ENSP00000331727.5

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64543 AN: 151504 Hom.: 16629 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.426 AC: 64650 AN: 151620 Hom.: 16677 Cov.: 31 AF XY: 0.432 AC XY: 32002 AN XY: 74072

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.375

Alfa AF: 0.299 Hom.: 7419

Bravo AF: 0.444

Asia WGS AF: 0.602 AC: 2088 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.51

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: rs1549020; hg19: chr2-163240847;