NM_012281.3:c.1115+58749C>T

Variant names:

• chr7-120334496-C-T
• rs10488286
• NM_012281.3:c.1115+58749C>T

Variant summary

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

The NM_012281.3(KCND2):​c.1115+58749C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,154 control chromosomes in the GnomAD database, including 1,111 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 0.12 (1111 hom., cov: 31)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1115+58749C>T		intron_variant	Intron 1 of 5	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1115+58749C>T		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.1115+58749C>T		intron_variant	Intron 1 of 5	1	NM_012281.3	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17760 AN: 152036 Hom.: 1113 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0666

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.117 AC: 17761 AN: 152154 Hom.: 1111 Cov.: 31 AF XY: 0.113 AC XY: 8393 AN XY: 74384

African (AFR) AF: 0.155 AC: 6437 AN: 41482

American (AMR) AF: 0.133 AC: 2040 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3472

East Asian (EAS) AF: 0.0664 AC: 344 AN: 5184

South Asian (SAS) AF: 0.0421 AC: 203 AN: 4820

European-Finnish (FIN) AF: 0.0741 AC: 785 AN: 10592

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7154 AN: 68006

Other (OTH) AF: 0.123 AC: 260 AN: 2110

Alfa AF: 0.110 Hom.: 149

Bravo AF: 0.125

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.73
DANN	Benign	0.56
PhyloP100		-0.11
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: rs10488286; hg19: chr7-119974550;