rs12673992

Positions:

• chr7-120732769-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012281.3(KCND2):​c.1116-134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 657,464 control chromosomes in the GnomAD database, including 37,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (14667 hom., cov: 32)
  • Exomes 𝑓: 0.29 (23303 hom.)
• Consequence: KCND2 NM_012281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.325

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-120732769-A-G is Benign according to our data. Variant chr7-120732769-A-G is described in ClinVar as [Benign]. Clinvar id is 1241406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCND2	NM_012281.3	c.1116-134A>G		intron_variant		ENST00000331113.9
KCND2	XM_047420346.1	c.1116-134A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCND2	ENST00000331113.9	c.1116-134A>G		intron_variant		1	NM_012281.3	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59686 AN: 151880 Hom.: 14611 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.286 AC: 144433 AN: 505466 Hom.: 23303 AF XY: 0.279 AC XY: 75568 AN XY: 270986

Gnomad4 AFR exome AF: 0.690

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.394 AC: 59816 AN: 151998 Hom.: 14667 Cov.: 32 AF XY: 0.395 AC XY: 29315 AN XY: 74290

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.359

Alfa AF: 0.275 Hom.: 4469

Bravo AF: 0.410

Asia WGS AF: 0.393 AC: 1362 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
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: rs12673992; hg19: chr7-120372823; COSMIC: COSV58606276;