chr7-120635907-A-G

Variant names:

• chr7-120635907-A-G
• rs17142876
• NM_012281.3:c.1116-96996A>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.1116-96996A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,162 control chromosomes in the GnomAD database, including 1,717 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 (1717 hom., cov: 32)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012281.3. 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.1116-96996A>G		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.1116-96996A>G		intron	N/A	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19293 AN: 152044 Hom.: 1710 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.127 AC: 19309 AN: 152162 Hom.: 1717 Cov.: 32 AF XY: 0.132 AC XY: 9839 AN XY: 74402

African (AFR) AF: 0.107 AC: 4462 AN: 41522

American (AMR) AF: 0.204 AC: 3116 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2365 AN: 5158

South Asian (SAS) AF: 0.0992 AC: 479 AN: 4830

European-Finnish (FIN) AF: 0.148 AC: 1570 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0972 AC: 6606 AN: 67992

Other (OTH) AF: 0.116 AC: 245 AN: 2112

Alfa AF: 0.0884 Hom.: 385

Bravo AF: 0.132

Asia WGS AF: 0.263 AC: 915 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		0.37
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: rs17142876; hg19: chr7-120275961;