7-120456657-C-T

Position:

• chr7-120456657-C-T

Variant summary

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

The NM_012281.3(KCND2):​c.1115+180910C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,192 control chromosomes in the GnomAD database, including 828 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 0.10 (828 hom., cov: 32)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1115+180910C>T		intron_variant		ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1115+180910C>T		intron_variant			XP_047276302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND2	ENST00000331113.9	c.1115+180910C>T		intron_variant		1	NM_012281.3	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15535 AN: 152074 Hom.: 830 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.102 AC: 15537 AN: 152192 Hom.: 828 Cov.: 32 AF XY: 0.0979 AC XY: 7288 AN XY: 74414

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0371

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.0730

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.111

Alfa AF: 0.100 Hom.: 82

Bravo AF: 0.108

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.23

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: rs917901; hg19: chr7-120096711;