1-110601792-ATATG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004974.4(KCNA2):c.*1487_*1490del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,108,042 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0017 (0 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-110601792-ATATG-A is Benign according to our data. Variant chr1-110601792-ATATG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1204366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00525 (733/139606) while in subpopulation AFR AF= 0.0171 (590/34568). AF 95% confidence interval is 0.0159. There are 2 homozygotes in gnomad4. There are 341 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 728 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4	c.*1487_*1490del		3_prime_UTR_variant	3/3	ENST00000316361.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA2	ENST00000316361.10	c.*1487_*1490del		3_prime_UTR_variant	3/3	2	NM_004974.4	P1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 728 AN: 139510 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00205

Gnomad EAS AF: 0.000215

Gnomad SAS AF: 0.000936

Gnomad FIN AF: 0.000105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00155

Gnomad OTH AF: 0.00205

GnomAD4 exome AF: 0.00173 AC: 1674 AN: 968436 Hom.: 0 AF XY: 0.00180 AC XY: 825 AN XY: 458630

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.00173

Gnomad4 SAS exome AF: 0.000655

Gnomad4 FIN exome AF: 0.00183

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.00525 AC: 733 AN: 139606 Hom.: 2 Cov.: 0 AF XY: 0.00504 AC XY: 341 AN XY: 67636

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00205

Gnomad4 EAS AF: 0.000216

Gnomad4 SAS AF: 0.000938

Gnomad4 FIN AF: 0.000105

Gnomad4 NFE AF: 0.00155

Gnomad4 OTH AF: 0.00203

Alfa AF: 0.00443 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1411300455; hg19: chr1-111144414;