rs7804315

Variant names:

• chr7-120631032-T-C
• rs7804315
• NM_012281.3:c.1116-101871T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-120631032-T-C
• chr7-120631032-T-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.1116-101871T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,978 control chromosomes in the GnomAD database, including 13,603 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 0.39 (13603 hom., cov: 33)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785
• Publications: 2 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=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1116-101871T>C		intron_variant	Intron 1 of 5	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1116-101871T>C		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.1116-101871T>C		intron_variant	Intron 1 of 5	1	NM_012281.3	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59072 AN: 151860 Hom.: 13553 Cov.: 33

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.389 AC: 59195 AN: 151978 Hom.: 13603 Cov.: 33 AF XY: 0.393 AC XY: 29166 AN XY: 74300

African (AFR) AF: 0.623 AC: 25849 AN: 41466

American (AMR) AF: 0.370 AC: 5654 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3468

East Asian (EAS) AF: 0.503 AC: 2601 AN: 5168

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4820

European-Finnish (FIN) AF: 0.388 AC: 4095 AN: 10562

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18061 AN: 67894

Other (OTH) AF: 0.325 AC: 687 AN: 2116

Alfa AF: 0.349 Hom.: 1331

Bravo AF: 0.400

Asia WGS AF: 0.385 AC: 1336 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		0.79
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: rs7804315; hg19: chr7-120271086;