1-110601828-G-GTGTGTGTGTGTGTA

Variant names:

• chr1-110601828-G-GTGTGTGTGTGTGTA
• rs763912060
• NM_004974.4:c.*1454_*1455insTACACACACACACA

Variant summary

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

The NM_004974.4(KCNA2):​c.*1454_*1455insTACACACACACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,242,958 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 0.0010 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00045 (0 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 145 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00100 AC: 144 AN: 143462 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000287

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00623

Gnomad SAS AF: 0.00250

Gnomad FIN AF: 0.00148

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000121

Gnomad OTH AF: 0.00151

GnomAD4 exome AF: 0.000448 AC: 492 AN: 1099420 Hom.: 0 Cov.: 27 AF XY: 0.000478 AC XY: 252 AN XY: 527464

Gnomad4 AFR exome AF: 0.000793

Gnomad4 AMR exome AF: 0.00316

Gnomad4 ASJ exome AF: 0.000435

Gnomad4 EAS exome AF: 0.00777

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.00160

Gnomad4 NFE exome AF: 0.000135

Gnomad4 OTH exome AF: 0.000797

GnomAD4 genome AF: 0.00101 AC: 145 AN: 143538 Hom.: 0 Cov.: 28 AF XY: 0.00112 AC XY: 78 AN XY: 69482

Gnomad4 AFR AF: 0.00198

Gnomad4 AMR AF: 0.000287

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00647

Gnomad4 SAS AF: 0.00251

Gnomad4 FIN AF: 0.00148

Gnomad4 NFE AF: 0.000121

Gnomad4 OTH AF: 0.00150

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;