7-120665095-G-A

Variant names:

• chr7-120665095-G-A
• rs728115
• NM_012281.3:c.1116-67808G>A

Variant summary

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

The ENST00000331113.9(KCND2):​c.1116-67808G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 151,948 control chromosomes in the GnomAD database, including 1,914 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 0.13 (1914 hom., cov: 32)
• Consequence: KCND2 ENST00000331113.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 9 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 = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000331113.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND2	NM_012281.3	MANE Select	c.1116-67808G>A		intron	N/A	NP_036413.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND2	ENST00000331113.9	TSL:1 MANE Select	c.1116-67808G>A		intron	N/A	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20256 AN: 151830 Hom.: 1907 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0863

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.133 AC: 20274 AN: 151948 Hom.: 1914 Cov.: 32 AF XY: 0.143 AC XY: 10583 AN XY: 74250

African (AFR) AF: 0.107 AC: 4461 AN: 41498

American (AMR) AF: 0.204 AC: 3111 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2177 AN: 5168

South Asian (SAS) AF: 0.0986 AC: 476 AN: 4826

European-Finnish (FIN) AF: 0.239 AC: 2518 AN: 10546

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0996 AC: 6758 AN: 67870

Other (OTH) AF: 0.118 AC: 248 AN: 2102

Alfa AF: 0.110 Hom.: 5388

Bravo AF: 0.132

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.72
PhyloP100		1.6
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: rs728115; hg19: chr7-120305149; COSMIC: COSV58606618;