2-162379935-A-T

Variant names:

• chr2-162379935-A-T
• rs2105402372
• NM_033272.4:c.3049T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033272.4(KCNH7):​c.3049T>A​(p.Trp1017Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W1017G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNH7 NM_033272.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4	c.3049T>A	p.Trp1017Arg	missense_variant	Exon 14 of 16	ENST00000332142.10	NP_150375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10	c.3049T>A	p.Trp1017Arg	missense_variant	Exon 14 of 16	1	NM_033272.4	ENSP00000331727.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.043	.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Uncertain	0.52	D
PhyloP100		4.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.12	.;N
REVEL	Uncertain	0.49
Sift	Benign	0.36	.;T
Sift4G	Benign	0.68	T;T
Polyphen		0.0030	.;B
Vest4		0.76
MutPred		0.30		.;Gain of solvent accessibility (P = 0.0133);
MVP		0.82
MPC		0.18
ClinPred		0.95	D
GERP RS		6.0
Varity_R		0.24
gMVP		0.26
Mutation Taster		=51/49	polymorphism

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: rs2105402372; hg19: chr2-163236445;