rs17142891

Variant names:

• chr7-120698554-G-A
• rs17142891
• NM_012281.3:c.1116-34349G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_012281.3(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 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477
• Publications: 1 publications found

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]

KCND2 Gene-Disease associations (from GenCC):

• KCND2-related neurodevelopmental disorder with or without seizures

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1116-34349G>A		intron_variant	Intron 1 of 5	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1116-34349G>A		intron_variant	Intron 2 of 6		XP_047276302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCND2	ENST00000331113.9	c.1116-34349G>A		intron_variant	Intron 1 of 5	1	NM_012281.3	ENSP00000333496.4

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

African (AFR) AF: 0.0162 AC: 673 AN: 41562

American (AMR) AF: 0.144 AC: 2203 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3468

East Asian (EAS) AF: 0.418 AC: 2154 AN: 5158

South Asian (SAS) AF: 0.0555 AC: 268 AN: 4830

European-Finnish (FIN) AF: 0.0658 AC: 697 AN: 10588

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0414 AC: 2819 AN: 68022

Other (OTH) AF: 0.0563 AC: 119 AN: 2114

Alfa AF: 0.0515 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
PhyloP100		0.48
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: rs17142891; hg19: chr7-120338608;