rs11971312

chr7-120684273-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012281.3(KCND2):c.1116-48630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 152,202 control chromosomes in the GnomAD database, including 234 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 0.041 (234 hom., cov: 32)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCND2	NM_012281.3	c.1116-48630A>G		intron_variant		ENST00000331113.9
KCND2	XM_047420346.1	c.1116-48630A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCND2	ENST00000331113.9	c.1116-48630A>G		intron_variant		1	NM_012281.3	P1

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6261 AN: 152084 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0413 AC: 6280 AN: 152202 Hom.: 234 Cov.: 32 AF XY: 0.0408 AC XY: 3034 AN XY: 74402

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.0180

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0160

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0345 Hom.: 21

Bravo AF: 0.0434

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	5.8
Dann	Benign	0.64

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: rs11971312; hg19: chr7-120324327;