rs7804315

Positions:

• chr7-120631032-T-C
• chr7-120631032-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1116-101871T>C		intron_variant		ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1116-101871T>C		intron_variant			XP_047276302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND2	ENST00000331113.9	c.1116-101871T>C		intron_variant		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

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.325

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7804315; hg19: chr7-120271086;