1-110601792-ATATGTG-A

Position:

• chr1-110601792-ATATGTG-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.*1485_*1490delCACATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,107,570 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (17 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (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]

KCNA2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-110601792-ATATGTG-A is Benign according to our data. Variant chr1-110601792-ATATGTG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1411/139586) while in subpopulation AFR AF= 0.0381 (1317/34546). AF 95% confidence interval is 0.0364. There are 17 homozygotes in gnomad4. There are 638 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1411 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1485_*1490delCACATA		3_prime_UTR_variant	3/3	ENST00000316361.10	NP_004965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNA2	ENST00000316361	c.*1485_*1490delCACATA		3_prime_UTR_variant	3/3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1407 AN: 139488 Hom.: 17 Cov.: 0

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00411

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000215

Gnomad SAS AF: 0.000936

Gnomad FIN AF: 0.000316

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000167

Gnomad OTH AF: 0.00924

GnomAD4 exome AF: 0.000996 AC: 964 AN: 967984 Hom.: 0 AF XY: 0.000892 AC XY: 409 AN XY: 458378

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.00218

Gnomad4 ASJ exome AF: 0.000398

Gnomad4 EAS exome AF: 0.000108

Gnomad4 SAS exome AF: 0.000273

Gnomad4 FIN exome AF: 0.00155

Gnomad4 NFE exome AF: 0.000258

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome AF: 0.0101 AC: 1411 AN: 139586 Hom.: 17 Cov.: 0 AF XY: 0.00943 AC XY: 638 AN XY: 67626

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.00411

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000216

Gnomad4 SAS AF: 0.000703

Gnomad4 FIN AF: 0.000316

Gnomad4 NFE AF: 0.000167

Gnomad4 OTH AF: 0.00916

Alfa AF: 0.00902 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 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1400312833; hg19: chr1-111144414;