7-120667164-C-T

Variant names:

• chr7-120667164-C-T
• rs4730972
• NM_012281.3:c.1116-65739C>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.1116-65739C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,772 control chromosomes in the GnomAD database, including 13,408 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 0.38 (13408 hom., cov: 32)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1116-65739C>T		intron_variant	Intron 1 of 5	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1116-65739C>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.1116-65739C>T		intron_variant	Intron 1 of 5	1	NM_012281.3	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58083 AN: 151654 Hom.: 13359 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.384 AC: 58208 AN: 151772 Hom.: 13408 Cov.: 32 AF XY: 0.386 AC XY: 28674 AN XY: 74190

African (AFR) AF: 0.622 AC: 25760 AN: 41416

American (AMR) AF: 0.367 AC: 5602 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2413 AN: 5172

South Asian (SAS) AF: 0.255 AC: 1227 AN: 4804

European-Finnish (FIN) AF: 0.383 AC: 4041 AN: 10540

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17451 AN: 67822

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.294 Hom.: 3589

Bravo AF: 0.394

Asia WGS AF: 0.383 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.1
DANN	Benign	0.63
PhyloP100		1.5
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: rs4730972; hg19: chr7-120307218;