rs397775888

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.2841-20dup 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:7
• 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]

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	UniProt
ATP1A2	NM_000702.4	c.2841-20dup		intron_variant		ENST00000361216.8
ATP1A2	XM_047421286.1	c.1950-20dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1A2	ENST00000361216.8	c.2841-20dup		intron_variant		1	NM_000702.4	P1
ATP1A2	ENST00000392233.7	c.2841-20dup		intron_variant		5
ATP1A2	ENST00000447527.1	c.1922-20dup		intron_variant		2
ATP1A2	ENST00000463989.1	n.177-20dup		intron_variant, non_coding_transcript_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:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, flagged submission	clinical testing	GeneDx	Jan 22, 2013	The variant is found in EPILEPSY panel(s). -
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;