Variant rs201244697 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_012281.3(KCND2):c.1375-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000869 in 1,611,756 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00087 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 1 hom. )

Consequence

KCND2
NM_012281.3 splice_region, intron

Scores

Splicing: ADA: 0.0002643

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.925

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:

KCND2 (HGNC:):

KCND2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 7-120742502-G-T is Benign according to our data. Variant chr7-120742502-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 460198.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 132 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND2	NM_012281.3 linkuse as main transcript	c.1375-8G>T		splice_region_variant, intron_variant		ENST00000331113.9	NP_036413.1	Q9NZV8A4D0V9
KCND2	XM_047420346.1 linkuse as main transcript	c.1375-8G>T		splice_region_variant, intron_variant			XP_047276302.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCND2	ENST00000331113.9 linkuse as main transcript	c.1375-8G>T	splice_region_variant, intron_variant		1	NM_012281.3	ENSP00000333496.4	Q9NZV8
KCND2	ENST00000425288.1 linkuse as main transcript	c.130-8G>T	splice_region_variant, intron_variant		4		ENSP00000415463.1	H7C445
KCND2	ENST00000473190.1 linkuse as main transcript	n.182G>T	non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.000868

AC:

132

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000661

AC:

166

AN:

251042

Hom.:

AF XY:

0.000708

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000855

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000869

AC:

1268

AN:

1459606

Hom.:

Cov.:

AF XY:

0.000811

AC XY:

589

AN XY:

726264

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.000713

GnomAD4 genome

AF:

0.000868

AC:

132

AN:

152150

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00334

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000762

Hom.:

Bravo

AF:

0.000914

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early myoclonic encephalopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.0

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