1-110601828-G-GTGTGTA

Position:

• chr1-110601828-G-GTGTGTA

Variant summary

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

The NM_004974.4(KCNA2):​c.*1454_*1455insTACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 1,230,850 control chromosomes in the GnomAD database, including 54 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (46 hom., cov: 28)
  • Exomes 𝑓: 0.0030 (8 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-GTGTGTA is Benign according to our data. Variant chr1-110601828-G-GTGTGTA is described in ClinVar as [Likely_benign]. Clinvar id is 1200267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1454_*1455insTACACA		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.*1454_*1455insTACACA		3_prime_UTR_variant	3/3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2001 AN: 143204 Hom.: 46 Cov.: 28

Gnomad AFR AF: 0.00656

Gnomad AMI AF: 0.00668

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.00938

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.00296

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.0157

GnomAD4 exome AF: 0.00300 AC: 3264 AN: 1087566 Hom.: 8 Cov.: 27 AF XY: 0.00314 AC XY: 1638 AN XY: 521892

Gnomad4 AFR exome AF: 0.00195

Gnomad4 AMR exome AF: 0.0357

Gnomad4 ASJ exome AF: 0.00528

Gnomad4 EAS exome AF: 0.0480

Gnomad4 SAS exome AF: 0.00319

Gnomad4 FIN exome AF: 0.00557

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.00394

GnomAD4 genome AF: 0.0140 AC: 2012 AN: 143284 Hom.: 46 Cov.: 28 AF XY: 0.0148 AC XY: 1024 AN XY: 69356

Gnomad4 AFR AF: 0.00675

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.00938

Gnomad4 EAS AF: 0.0726

Gnomad4 SAS AF: 0.0213

Gnomad4 FIN AF: 0.00296

Gnomad4 NFE AF: 0.00889

Gnomad4 OTH AF: 0.0150

Alfa AF: 0.000802 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 10, 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;