rs149560146

Variant names:

• chr1-110601777-AATATATAT-A
• rs149560146
• NM_004974.4:c.*1498_*1505delATATATAT

Your query was ambiguous. Multiple possible variants found:

• chr1-110601777-AATATATAT-A
• chr1-110601777-AATATATAT-AAT
• chr1-110601777-AATATATAT-AATAT
• chr1-110601777-AATATATAT-AATATAT
• chr1-110601777-AATATATAT-AATATATATAT
• chr1-110601777-AATATATAT-AATATATATATAT
• chr1-110601777-AATATATAT-AATATATATATATAT
• chr1-110601777-AATATATAT-AATATATATATATATAT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004974.4(KCNA2):​c.*1498_*1505delATATATAT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000323 in 990,608 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 22)
  • Exomes 𝑓: 0.00037 (2 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93
• Publications: 0 publications found

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]

KCNA2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 32

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1498_*1505delATATATAT		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	ENST00000316361.10	c.*1498_*1505delATATATAT		3_prime_UTR_variant	Exon 3 of 3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.0000356 AC: 5 AN: 140432 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000427

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000371 AC: 315 AN: 850176 Hom.: 2 AF XY: 0.000322 AC XY: 129 AN XY: 400830

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00296 AC: 51 AN: 17252

American (AMR) AF: 0.000812 AC: 5 AN: 6158

Ashkenazi Jewish (ASJ) AF: 0.000786 AC: 8 AN: 10178

East Asian (EAS) AF: 0.00122 AC: 22 AN: 18104

South Asian (SAS) AF: 0.00339 AC: 52 AN: 15360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11310

Middle Eastern (MID) AF: 0.00274 AC: 6 AN: 2186

European-Non Finnish (NFE) AF: 0.000198 AC: 146 AN: 736994

Other (OTH) AF: 0.000766 AC: 25 AN: 32634

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000356 AC: 5 AN: 140432 Hom.: 0 Cov.: 22 AF XY: 0.0000443 AC XY: 3 AN XY: 67746

African (AFR) AF: 0.0000800 AC: 3 AN: 37500

American (AMR) AF: 0.00 AC: 0 AN: 13914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3368

East Asian (EAS) AF: 0.000427 AC: 2 AN: 4686

South Asian (SAS) AF: 0.00 AC: 0 AN: 4176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64772

Other (OTH) AF: 0.00 AC: 0 AN: 1914

Alfa AF: 0.00 Hom.: 99

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

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

Other links and lift over

dbSNP: rs149560146; hg19: chr1-111144399;