rs17142891

Positions:

• chr7-120698554-G-A
• chr7-120698554-G-C

Variant summary

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

The ENST00000331113.9(KCND2):​c.1116-34349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 152,230 control chromosomes in the GnomAD database, including 772 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 0.060 (772 hom., cov: 32)
• Consequence: KCND2 ENST00000331113.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1116-34349G>A		intron_variant		ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1116-34349G>A		intron_variant			XP_047276302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND2	ENST00000331113.9	c.1116-34349G>A		intron_variant		1	NM_012281.3	ENSP00000333496	P1

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9196 AN: 152112 Hom.: 770 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00991

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0578

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

GnomAD4 genome AF: 0.0605 AC: 9204 AN: 152230 Hom.: 772 Cov.: 32 AF XY: 0.0654 AC XY: 4865 AN XY: 74426

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.0555

Gnomad4 FIN AF: 0.0658

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0530 Hom.: 40

Bravo AF: 0.0674

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.47

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: rs17142891; hg19: chr7-120338608;