Variant rs12673992 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.325

Variant links:

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]

KCND2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
KCND2	NM_012281.3 linkuse as main transcript	c.1116-134A>G		intron_variant		ENST00000331113.9	NP_036413.1	Q9NZV8A4D0V9
KCND2	XM_047420346.1 linkuse as main transcript	c.1116-134A>G		intron_variant			XP_047276302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND2	ENST00000331113.9 linkuse as main transcript	c.1116-134A>G		intron_variant		1	NM_012281.3	ENSP00000333496.4		Q9NZV8

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59686

AN:

151880

Hom.:

14611

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.395

AC XY:

29315

AN XY:

74290

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over