Variant 1-110601792-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.*1491T>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 0.105 in 138,166 control chromosomes in the GnomAD database, including 1,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1162 hom., cov: 27)

Exomes 𝑓: 0.028 ( 1945 hom. )

Failed GnomAD Quality Control

Consequence

KCNA2
NM_004974.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0400

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 1-110601792-A-G is Benign according to our data. Variant chr1-110601792-A-G is described in ClinVar as [Benign]. Clinvar id is 1289753.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4 linkuse as main transcript	c.*1491T>C		3_prime_UTR_variant	3/3	ENST00000316361.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA2	ENST00000316361.10 linkuse as main transcript	c.*1491T>C		3_prime_UTR_variant	3/3	2	NM_004974.4	P1	P16389-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

14547

AN:

138066

Hom.:

1150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.0558

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.0637

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0530

Gnomad NFE

AF:

0.0580

Gnomad OTH

AF:

0.112

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0284

AC:

26952

AN:

949996

Hom.:

1945

Cov.:

AF XY:

0.0289

AC XY:

13019

AN XY:

449938

show subpopulations

Gnomad4 AFR exome

AF:

0.0413

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.0398

Gnomad4 EAS exome

AF:

0.340

Gnomad4 SAS exome

AF:

0.0422

Gnomad4 FIN exome

AF:

0.0850

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0418

GnomAD4 genome

AF:

0.105

AC:

14575

AN:

138166

Hom.:

1162

Cov.:

AF XY:

0.113

AC XY:

7540

AN XY:

66852

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.0637

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0580

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.0329

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

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.9

DANN

Benign

0.39

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