2-162559852-A-G

Variant names:

• chr2-162559852-A-G
• rs901304
• NM_033272.4:c.308-22772T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033272.4(KCNH7):​c.308-22772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,038 control chromosomes in the GnomAD database, including 15,850 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 0.38 (15850 hom., cov: 32)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 7 publications found

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]

KCNH7 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033272.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	NM_033272.4	MANE Select	c.308-22772T>C		intron	N/A	NP_150375.2
	KCNH7	NM_173162.3		c.308-22772T>C		intron	N/A	NP_775185.1	Q9NS40-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	ENST00000332142.10	TSL:1 MANE Select	c.308-22772T>C		intron	N/A	ENSP00000331727.5	Q9NS40-1
	KCNH7	ENST00000328032.8	TSL:1	c.308-22772T>C		intron	N/A	ENSP00000333781.4	Q9NS40-2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58208 AN: 151920 Hom.: 15793 Cov.: 32

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.384 AC: 58337 AN: 152038 Hom.: 15850 Cov.: 32 AF XY: 0.386 AC XY: 28658 AN XY: 74330

African (AFR) AF: 0.754 AC: 31258 AN: 41470

American (AMR) AF: 0.418 AC: 6383 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2649 AN: 5150

South Asian (SAS) AF: 0.271 AC: 1302 AN: 4812

European-Finnish (FIN) AF: 0.247 AC: 2614 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12476 AN: 67972

Other (OTH) AF: 0.343 AC: 726 AN: 2116

Alfa AF: 0.274 Hom.: 13412

Bravo AF: 0.419

Asia WGS AF: 0.420 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.068
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs901304; hg19: chr2-163416362;