NM_004974.4:c.*1487_*1488delCA

Variant names:

• chr1-110601794-ATG-A
• rs35728918
• NM_004974.4:c.*1487_*1488delCA

Variant summary

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

The NM_004974.4(KCNA2):​c.*1487_*1488delCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 803,640 control chromosomes in the GnomAD database, including 508 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (461 hom., cov: 0)
  • Exomes 𝑓: 0.062 (47 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.391

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 1-110601794-ATG-A is Benign according to our data. Variant chr1-110601794-ATG-A is described in ClinVar as [Benign]. Clinvar id is 1251556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1487_*1488delCA		3_prime_UTR_variant	Exon 3 of 3	ENST00000316361.10	NP_004965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNA2	ENST00000316361	c.*1487_*1488delCA		3_prime_UTR_variant	Exon 3 of 3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 9194 AN: 135554 Hom.: 461 Cov.: 0

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.0850

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0588

GnomAD4 exome AF: 0.0620 AC: 41387 AN: 668038 Hom.: 47 AF XY: 0.0628 AC XY: 20046 AN XY: 318978

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.0759

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0649

Gnomad4 SAS exome AF: 0.0661

Gnomad4 FIN exome AF: 0.0964

Gnomad4 NFE exome AF: 0.0569

Gnomad4 OTH exome AF: 0.0755

GnomAD4 genome AF: 0.0679 AC: 9204 AN: 135602 Hom.: 461 Cov.: 0 AF XY: 0.0682 AC XY: 4453 AN XY: 65254

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0796

Gnomad4 EAS AF: 0.0574

Gnomad4 SAS AF: 0.0312

Gnomad4 FIN AF: 0.0370

Gnomad4 NFE AF: 0.0334

Gnomad4 OTH AF: 0.0589

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs35728918; hg19: chr1-111144416;