rs12673992

Variant names:

• chr7-120732769-A-G
• rs12673992
• NM_012281.3:c.1116-134A>G

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCND2	NM_012281.3	c.1116-134A>G		intron_variant	Intron 1 of 5	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.1116-134A>G		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.1116-134A>G		intron_variant	Intron 1 of 5	1	NM_012281.3	ENSP00000333496.4

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 AC: 9164 AN: 13288

Gnomad4 AMR exome AF: 0.386 AC: 8143 AN: 21094

Gnomad4 ASJ exome AF: 0.201 AC: 3235 AN: 16066

Gnomad4 EAS exome AF: 0.506 AC: 15716 AN: 31080

Gnomad4 SAS exome AF: 0.244 AC: 11344 AN: 46460

Gnomad4 FIN exome AF: 0.360 AC: 12886 AN: 35836

Gnomad4 NFE exome AF: 0.241 AC: 75138 AN: 311520

Gnomad4 Remaining exome AF: 0.296 AC: 8270 AN: 27966

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 AC: 0.690474 AN: 0.690474

Gnomad4 AMR AF: 0.346 AC: 0.345846 AN: 0.345846

Gnomad4 ASJ AF: 0.215 AC: 0.21515 AN: 0.21515

Gnomad4 EAS AF: 0.468 AC: 0.467711 AN: 0.467711

Gnomad4 SAS AF: 0.249 AC: 0.248545 AN: 0.248545

Gnomad4 FIN AF: 0.374 AC: 0.374028 AN: 0.374028

Gnomad4 NFE AF: 0.242 AC: 0.241798 AN: 0.241798

Gnomad4 OTH AF: 0.359 AC: 0.358974 AN: 0.358974

Alfa AF: 0.281 Hom.: 5215

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

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.64
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

Publications

LitVar

Other links and lift over

dbSNP: rs12673992; hg19: chr7-120372823; COSMIC: COSV58606276;