7-120740853-C-T

Variant names:

• chr7-120740853-C-T
• rs6975107
• NM_012281.3:c.1279-681C>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.1279-681C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 456,036 control chromosomes in the GnomAD database, including 531 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 0.042 (442 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (89 hom.)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 1 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 (REVEL=0.004).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 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.1279-681C>T		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.1279-681C>T		intron	N/A	ENSP00000333496.4
	KCND2	ENST00000425288.1	TSL:4	c.8C>T	p.Ser3Leu	missense	Exon 1 of 5	ENSP00000415463.1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6316 AN: 152014 Hom.: 442 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0326

GnomAD2 exomes AF: 0.00997 AC: 1356 AN: 135974 AF XY: 0.00836

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.00663

Gnomad ASJ exome AF: 0.00435

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000811

Gnomad OTH exome AF: 0.00746

GnomAD4 exome AF: 0.00689 AC: 2094 AN: 303906 Hom.: 89 Cov.: 0 AF XY: 0.00590 AC XY: 1022 AN XY: 173078

African (AFR) AF: 0.137 AC: 1170 AN: 8558

American (AMR) AF: 0.00708 AC: 193 AN: 27258

Ashkenazi Jewish (ASJ) AF: 0.00380 AC: 41 AN: 10784

East Asian (EAS) AF: 0.00 AC: 0 AN: 9204

South Asian (SAS) AF: 0.00721 AC: 430 AN: 59642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12790

Middle Eastern (MID) AF: 0.00755 AC: 21 AN: 2780

European-Non Finnish (NFE) AF: 0.000511 AC: 81 AN: 158660

Other (OTH) AF: 0.0111 AC: 158 AN: 14230

GnomAD4 genome AF: 0.0416 AC: 6331 AN: 152130 Hom.: 442 Cov.: 32 AF XY: 0.0402 AC XY: 2990 AN XY: 74358

African (AFR) AF: 0.142 AC: 5887 AN: 41506

American (AMR) AF: 0.0173 AC: 264 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00890 AC: 43 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 67976

Other (OTH) AF: 0.0322 AC: 68 AN: 2110

Alfa AF: 0.0402 Hom.: 204

Bravo AF: 0.0478

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.59
PhyloP100		-1.9
PromoterAI		-0.0075	Neutral
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: rs6975107; hg19: chr7-120380907;