rs7807053

Variant names:

• chr7-120710453-G-T
• rs7807053
• NM_012281.3:c.1116-22450G>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.1116-22450G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 152,122 control chromosomes in the GnomAD database, including 331 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 0.056 (331 hom., cov: 32)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1116-22450G>T		intron_variant	Intron 1 of 5	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1116-22450G>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.1116-22450G>T		intron_variant	Intron 1 of 5	1	NM_012281.3	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8567 AN: 152004 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.0964

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.0677

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

GnomAD4 genome AF: 0.0563 AC: 8561 AN: 152122 Hom.: 331 Cov.: 32 AF XY: 0.0553 AC XY: 4115 AN XY: 74366

African (AFR) AF: 0.0158 AC: 656 AN: 41526

American (AMR) AF: 0.0772 AC: 1178 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 334 AN: 3466

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4816

European-Finnish (FIN) AF: 0.0522 AC: 553 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0812 AC: 5520 AN: 67976

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.0729 Hom.: 251

Bravo AF: 0.0584

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.34
PhyloP100		0.77
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: rs7807053; hg19: chr7-120350507;