1-160139618-A-AC

Position:

• chr1-160139618-A-AC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000702.4(ATP1A2):​c.2841-20dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,610,610 control chromosomes in the GnomAD database, including 14,940 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1371 hom., cov: 30)
  • Exomes 𝑓: 0.13 (13569 hom.)
• Consequence: ATP1A2 NM_000702.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.261

Genes affected

ATP1A2 (HGNC:800): (ATPase Na+/K+ transporting subunit alpha 2) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 2 subunit. Mutations in this gene result in familial basilar or hemiplegic migraines, and in a rare syndrome known as alternating hemiplegia of childhood. [provided by RefSeq, Oct 2008]

ATP1A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-160139618-A-AC is Benign according to our data. Variant chr1-160139618-A-AC is described in ClinVar as [Benign]. Clinvar id is 204875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1A2	NM_000702.4	c.2841-20dupC		intron_variant		ENST00000361216.8	NP_000693.1
ATP1A2	XM_047421286.1	c.1950-20dupC		intron_variant			XP_047277242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1A2	ENST00000361216.8	c.2841-20dupC		intron_variant		1	NM_000702.4	ENSP00000354490.3
ATP1A2	ENST00000392233.7	c.2841-20dupC		intron_variant		5		ENSP00000376066.3
ATP1A2	ENST00000447527.1	c.1920-20dupC		intron_variant		2		ENSP00000411705.1
ATP1A2	ENST00000463989.1	n.177-20dupC		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19831 AN: 151786 Hom.: 1369 Cov.: 30

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.131 AC: 32802 AN: 251090 Hom.: 2373 AF XY: 0.129 AC XY: 17530 AN XY: 135722

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.0608

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.133 AC: 194623 AN: 1458706 Hom.: 13569 Cov.: 32 AF XY: 0.133 AC XY: 96650 AN XY: 725876

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0497

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.131 AC: 19841 AN: 151904 Hom.: 1371 Cov.: 30 AF XY: 0.132 AC XY: 9816 AN XY: 74228

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.127

Alfa AF: 0.139 Hom.: 350

Bravo AF: 0.122

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, flagged submission	clinical testing	GeneDx	Jan 22, 2013	The variant is found in EPILEPSY panel(s). -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 23. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Developmental and epileptic encephalopathy 98 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Migraine, familial hemiplegic, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Alternating hemiplegia of childhood 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs397775888; hg19: chr1-160109408;