NM_012281.3:c.1116-49230A>G

Variant names:

• chr7-120683673-A-G
• rs7795646
• NM_012281.3:c.1116-49230A>G

Variant summary

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

The NM_012281.3(KCND2):​c.1116-49230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,954 control chromosomes in the GnomAD database, including 9,907 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 0.34 (9907 hom., cov: 32)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1116-49230A>G		intron_variant	Intron 1 of 5	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1116-49230A>G		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.1116-49230A>G		intron_variant	Intron 1 of 5	1	NM_012281.3	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51349 AN: 151836 Hom.: 9880 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.339 AC: 51439 AN: 151954 Hom.: 9907 Cov.: 32 AF XY: 0.343 AC XY: 25490 AN XY: 74266

African (AFR) AF: 0.504 AC: 20880 AN: 41448

American (AMR) AF: 0.342 AC: 5207 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2315 AN: 5164

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4824

European-Finnish (FIN) AF: 0.375 AC: 3958 AN: 10552

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16456 AN: 67942

Other (OTH) AF: 0.282 AC: 595 AN: 2112

Alfa AF: 0.271 Hom.: 12221

Bravo AF: 0.345

Asia WGS AF: 0.352 AC: 1224 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.67
PhyloP100		0.38
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: rs7795646; hg19: chr7-120323727;