1-110601828-G-GTA

Position:

• chr1-110601828-G-GTA

Variant summary

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

The NM_004974.4(KCNA2):​c.*1453_*1454dupTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00721 in 1,225,606 control chromosomes in the GnomAD database, including 171 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (10 hom., cov: 28)
  • Exomes 𝑓: 0.0073 (161 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600

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 1-110601828-G-GTA is Benign according to our data. Variant chr1-110601828-G-GTA is described in ClinVar as [Likely_benign]. Clinvar id is 1212933.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00628 (902/143552) while in subpopulation AFR AF= 0.0196 (753/38352). AF 95% confidence interval is 0.0185. There are 10 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 902 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1453_*1454dupTA		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.*1453_*1454dupTA		3_prime_UTR_variant	3/3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 899 AN: 143474 Hom.: 10 Cov.: 28

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00467

Gnomad ASJ AF: 0.00468

Gnomad EAS AF: 0.00400

Gnomad SAS AF: 0.00227

Gnomad FIN AF: 0.000634

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000347

Gnomad OTH AF: 0.00554

GnomAD4 exome AF: 0.00734 AC: 7939 AN: 1082054 Hom.: 161 Cov.: 27 AF XY: 0.00721 AC XY: 3744 AN XY: 519248

Gnomad4 AFR exome AF: 0.0260

Gnomad4 AMR exome AF: 0.0246

Gnomad4 ASJ exome AF: 0.00673

Gnomad4 EAS exome AF: 0.0211

Gnomad4 SAS exome AF: 0.0194

Gnomad4 FIN exome AF: 0.00556

Gnomad4 NFE exome AF: 0.00581

Gnomad4 OTH exome AF: 0.00992

GnomAD4 genome AF: 0.00628 AC: 902 AN: 143552 Hom.: 10 Cov.: 28 AF XY: 0.00619 AC XY: 430 AN XY: 69486

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.00459

Gnomad4 ASJ AF: 0.00468

Gnomad4 EAS AF: 0.00401

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000634

Gnomad4 NFE AF: 0.000347

Gnomad4 OTH AF: 0.00551

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553181014; hg19: chr1-111144450;