1-110601794-ATGTGTGTGTGTGTGTGTGTGTG-ATGTGTGTGTGTG

Variant names:

• chr1-110601794-ATGTGTGTGTG-A
• rs35728918
• NM_004974.4:c.*1479_*1488delCACACACACA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004974.4(KCNA2):​c.*1479_*1488delCACACACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 840,360 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00097 (0 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1479_*1488delCACACACACA		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.*1479_*1488delCACACACACA		3_prime_UTR_variant	Exon 3 of 3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 190 AN: 135924 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00318

Gnomad AMI AF: 0.00114

Gnomad AMR AF: 0.00149

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.000245

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00680

Gnomad NFE AF: 0.000709

Gnomad OTH AF: 0.00213

GnomAD4 exome AF: 0.000974 AC: 686 AN: 704388 Hom.: 0 AF XY: 0.00102 AC XY: 345 AN XY: 336608

Gnomad4 AFR exome AF: 0.00321

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.000432

Gnomad4 EAS exome AF: 0.00667

Gnomad4 SAS exome AF: 0.0000790

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000794

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00140 AC: 190 AN: 135972 Hom.: 0 Cov.: 0 AF XY: 0.00151 AC XY: 99 AN XY: 65458

Gnomad4 AFR AF: 0.00317

Gnomad4 AMR AF: 0.00149

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00157

Gnomad4 SAS AF: 0.000246

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000709

Gnomad4 OTH AF: 0.00211

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: rs35728918; hg19: chr1-111144416;