rs7807053

chr7-120710453-G-T

Variant summary

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

The NM_012281.3(KCND2):c.1116-22450G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 152,122 control chromosomes in the GnomAD database, including 331 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 0.056 (331 hom., cov: 32)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769

Genes affected

KCND2 (HGNC:6238): (potassium voltage-gated channel subfamily D member 2) 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCND2	NM_012281.3	c.1116-22450G>T		intron_variant		ENST00000331113.9
KCND2	XM_047420346.1	c.1116-22450G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCND2	ENST00000331113.9	c.1116-22450G>T		intron_variant		1	NM_012281.3	P1

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8567 AN: 152004 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.0964

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.0677

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

GnomAD4 genome AF: 0.0563 AC: 8561 AN: 152122 Hom.: 331 Cov.: 32 AF XY: 0.0553 AC XY: 4115 AN XY: 74366

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.0964

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0522

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.0670

Alfa AF: 0.0717 Hom.: 224

Bravo AF: 0.0584

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.5
Dann	Benign	0.34

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: rs7807053; hg19: chr7-120350507;