1-110601828-G-GTGTGTGTGTA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004974.4(KCNA2):c.*1454_*1455insTACACACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,239,200 control chromosomes in the GnomAD database, including 28 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (27 hom., cov: 28)
  • Exomes 𝑓: 0.0018 (1 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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-110601828-G-GTGTGTGTGTA is Benign according to our data. Variant chr1-110601828-G-GTGTGTGTGTA is described in ClinVar as [Likely_benign]. Clinvar id is 1213655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4	c.*1454_*1455insTACACACACA		3_prime_UTR_variant	3/3	ENST00000316361.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA2	ENST00000316361.10	c.*1454_*1455insTACACACACA		3_prime_UTR_variant	3/3	2	NM_004974.4	P1

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2528 AN: 142862 Hom.: 27 Cov.: 28

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.0297

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.00884

Gnomad OTH AF: 0.0218

GnomAD4 exome AF: 0.00183 AC: 2004 AN: 1096264 Hom.: 1 Cov.: 27 AF XY: 0.00199 AC XY: 1049 AN XY: 525922

Gnomad4 AFR exome AF: 0.00633

Gnomad4 AMR exome AF: 0.00804

Gnomad4 ASJ exome AF: 0.000187

Gnomad4 EAS exome AF: 0.0278

Gnomad4 SAS exome AF: 0.00255

Gnomad4 FIN exome AF: 0.00943

Gnomad4 NFE exome AF: 0.000742

Gnomad4 OTH exome AF: 0.00360

GnomAD4 genome AF: 0.0177 AC: 2529 AN: 142936 Hom.: 27 Cov.: 28 AF XY: 0.0186 AC XY: 1288 AN XY: 69210

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.0596

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.00885

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.00414 Hom.: 10

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 21, 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: rs763912060; hg19: chr1-111144450;