1-110601792-A-ATG

Position:

• chr1-110601792-A-ATG

Variant summary

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

The NM_004974.4(KCNA2):​c.*1490_*1491insCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 139,420 control chromosomes in the GnomAD database, including 41 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (41 hom., cov: 29)
  • Exomes 𝑓: 0.012 (3 hom.)
  • Failed GnomAD Quality Control
• 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-A-ATG is Benign according to our data. Variant chr1-110601792-A-ATG is described in ClinVar as [Likely_benign]. Clinvar id is 1201388.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0216 (3006/139420) while in subpopulation NFE AF= 0.0281 (1847/65822). AF 95% confidence interval is 0.027. There are 41 homozygotes in gnomad4. There are 1498 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3006 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4	c.*1490_*1491insCA		3_prime_UTR_variant	3/3	ENST00000316361.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA2	ENST00000316361.10	c.*1490_*1491insCA		3_prime_UTR_variant	3/3	2	NM_004974.4	P1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3003 AN: 139322 Hom.: 41 Cov.: 29

Gnomad AFR AF: 0.00679

Gnomad AMI AF: 0.0375

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.0397

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0149

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0121 AC: 11608 AN: 959578 Hom.: 3 Cov.: 18 AF XY: 0.0124 AC XY: 5626 AN XY: 454412

Gnomad4 AFR exome AF: 0.00299

Gnomad4 AMR exome AF: 0.00929

Gnomad4 ASJ exome AF: 0.0122

Gnomad4 EAS exome AF: 0.00146

Gnomad4 SAS exome AF: 0.00897

Gnomad4 FIN exome AF: 0.0325

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.0216 AC: 3006 AN: 139420 Hom.: 41 Cov.: 29 AF XY: 0.0222 AC XY: 1498 AN XY: 67548

Gnomad4 AFR AF: 0.00688

Gnomad4 AMR AF: 0.0206

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0435

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.0148

Alfa AF: 0.00962 Hom.: 3

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

Jan 22, 2020

- -

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: rs1379102271; hg19: chr1-111144414;