1-110601794-ATGTGTGTGTGTGTGTGTGTGTG-ATGTGTGTGTGTGTGTG

Variant names:

• chr1-110601794-ATGTGTG-A
• rs35728918
• NM_004974.4:c.*1483_*1488delCACACA

Variant summary

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

The NM_004974.4(KCNA2):​c.*1483_*1488delCACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 839,222 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0036 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0050 (3 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 489 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1483_*1488delCACACA		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.*1483_*1488delCACACA		3_prime_UTR_variant	Exon 3 of 3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.00360 AC: 489 AN: 135918 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.0114

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00330

Gnomad EAS AF: 0.00268

Gnomad SAS AF: 0.00245

Gnomad FIN AF: 0.00191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00438

Gnomad OTH AF: 0.00266

GnomAD4 exome AF: 0.00503 AC: 3539 AN: 703256 Hom.: 3 AF XY: 0.00502 AC XY: 1686 AN XY: 336096

Gnomad4 AFR exome AF: 0.00274

Gnomad4 AMR exome AF: 0.00507

Gnomad4 ASJ exome AF: 0.00368

Gnomad4 EAS exome AF: 0.000834

Gnomad4 SAS exome AF: 0.00475

Gnomad4 FIN exome AF: 0.00625

Gnomad4 NFE exome AF: 0.00520

Gnomad4 OTH exome AF: 0.00496

GnomAD4 genome AF: 0.00360 AC: 489 AN: 135966 Hom.: 2 Cov.: 0 AF XY: 0.00353 AC XY: 231 AN XY: 65452

Gnomad4 AFR AF: 0.00221

Gnomad4 AMR AF: 0.00483

Gnomad4 ASJ AF: 0.00330

Gnomad4 EAS AF: 0.00269

Gnomad4 SAS AF: 0.00246

Gnomad4 FIN AF: 0.00191

Gnomad4 NFE AF: 0.00438

Gnomad4 OTH AF: 0.00264

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;