NM_004974.4:c.*1454_*1455insTACA

Variant names:

• chr1-110601828-G-GTGTA
• rs763912060
• NM_004974.4:c.*1454_*1455insTACA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004974.4(KCNA2):​c.*1454_*1455insTACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,237,206 control chromosomes in the GnomAD database, including 14 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0044 (12 hom., cov: 28)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00437 (628/143554) while in subpopulation EAS AF= 0.0451 (202/4476). AF 95% confidence interval is 0.04. There are 12 homozygotes in gnomad4. There are 311 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 628 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1454_*1455insTACA		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.*1454_*1455insTACA		3_prime_UTR_variant	Exon 3 of 3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.00433 AC: 621 AN: 143478 Hom.: 11 Cov.: 28

Gnomad AFR AF: 0.00272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00380

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.00273

Gnomad FIN AF: 0.00338

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.00404

GnomAD4 exome AF: 0.00133 AC: 1458 AN: 1093652 Hom.: 2 Cov.: 27 AF XY: 0.00138 AC XY: 726 AN XY: 524810

Gnomad4 AFR exome AF: 0.000886

Gnomad4 AMR exome AF: 0.00934

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.0281

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.00329

Gnomad4 NFE exome AF: 0.000543

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00437 AC: 628 AN: 143554 Hom.: 12 Cov.: 28 AF XY: 0.00447 AC XY: 311 AN XY: 69500

Gnomad4 AFR AF: 0.00276

Gnomad4 AMR AF: 0.00912

Gnomad4 ASJ AF: 0.00380

Gnomad4 EAS AF: 0.0451

Gnomad4 SAS AF: 0.00296

Gnomad4 FIN AF: 0.00338

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.00351

Alfa AF: 0.00154 Hom.: 10

ClinVar

Not reported in ClinVar

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;