1-110593985-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_004974.4(KCNA2):​c.*9298G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,547,722 control chromosomes in the GnomAD database, including 1,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 750 hom., cov: 30)
Exomes 𝑓: 0.0055 ( 644 hom. )

Consequence

KCNA2
NM_004974.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.52
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 1-110593985-C-T is Benign according to our data. Variant chr1-110593985-C-T is described in ClinVar as [Benign]. Clinvar id is 1237563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNA2NM_004974.4 linkc.*9298G>A 3_prime_UTR_variant Exon 3 of 3 ENST00000316361.10 NP_004965.1 P16389-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNA2ENST00000316361 linkc.*9298G>A 3_prime_UTR_variant Exon 3 of 3 2 NM_004974.4 ENSP00000314520.4 P16389-1

Frequencies

GnomAD3 genomes
AF:
0.0530
AC:
8058
AN:
152086
Hom.:
746
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.184
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0190
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000632
Gnomad OTH
AF:
0.0407
GnomAD4 exome
AF:
0.00546
AC:
7620
AN:
1395518
Hom.:
644
Cov.:
30
AF XY:
0.00473
AC XY:
3259
AN XY:
688306
show subpopulations
Gnomad4 AFR exome
AF:
0.192
Gnomad4 AMR exome
AF:
0.00952
Gnomad4 ASJ exome
AF:
0.0000399
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000470
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000361
Gnomad4 OTH exome
AF:
0.0131
GnomAD4 genome
AF:
0.0531
AC:
8078
AN:
152204
Hom.:
750
Cov.:
30
AF XY:
0.0513
AC XY:
3818
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.184
Gnomad4 AMR
AF:
0.0190
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000632
Gnomad4 OTH
AF:
0.0402
Alfa
AF:
0.0109
Hom.:
101
Bravo
AF:
0.0601
Asia WGS
AF:
0.00866
AC:
31
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 26, 2018
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
-0.38
CADD
Benign
19
DANN
Benign
0.78

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.

Other links and lift over

dbSNP: rs12096011; hg19: chr1-111136607; API