Variant 1-110601790-A-G 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_004974.4(KCNA2):c.*1493T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 1,139,810 control chromosomes in the GnomAD database, including 2,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.099 ( 1082 hom., cov: 28)

Exomes 𝑓: 0.024 ( 1509 hom. )

Consequence

KCNA2
NM_004974.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.146

Variant links:

Genes affected

KCNA2 (HGNC:6220): (potassium voltage-gated channel subfamily A member 2) Potassium 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, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1. [provided by RefSeq, Jul 2008]

KCNA2 links:

KCNA2 (HGNC:):

KCNA2 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=-0.91).

BP6

Variant 1-110601790-A-G is Benign according to our data. Variant chr1-110601790-A-G is described in ClinVar as [Benign]. Clinvar id is 1269688.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA2	NM_004974.4 linkuse as main transcript	c.*1493T>C		3_prime_UTR_variant	3/3	ENST00000316361.10	NP_004965.1	P16389-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNA2	ENST00000316361 linkuse as main transcript	c.*1493T>C		3_prime_UTR_variant	3/3	2	NM_004974.4	ENSP00000314520.4		P16389-1

Frequencies

GnomAD3 genomes

AF:

0.0988

AC:

13489

AN:

136590

Hom.:

1070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0758

Gnomad AMI

AF:

0.0566

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.0636

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0500

Gnomad NFE

AF:

0.0578

Gnomad OTH

AF:

0.109

GnomAD4 exome

AF:

0.0236

AC:

23650

AN:

1003134

Hom.:

1509

Cov.:

AF XY:

0.0242

AC XY:

11489

AN XY:

475262

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.0342

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.0349

Gnomad4 FIN exome

AF:

0.0744

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0988

AC:

13508

AN:

136676

Hom.:

1082

Cov.:

AF XY:

0.106

AC XY:

7025

AN XY:

66112

show subpopulations

Gnomad4 AFR

AF:

0.0758

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.0636

Gnomad4 EAS

AF:

0.356

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0578

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0820

Hom.:

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

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

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