rs373796693

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000702.4(ATP1A2):c.13-11_13-8del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 1,573,876 control chromosomes in the GnomAD database, including 516,775 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42415 hom., cov: 0)

Exomes 𝑓: 0.81 ( 474360 hom. )

Consequence

ATP1A2
NM_000702.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.88

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-160120891-CCCTT-C is Benign according to our data. Variant chr1-160120891-CCCTT-C is described in ClinVar as [Benign]. Clinvar id is 166705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-160120891-CCCTT-C is described in Lovd as [Benign]. Variant chr1-160120891-CCCTT-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1A2	NM_000702.4 linkuse as main transcript	c.13-11_13-8del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000361216.8	NP_000693.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ATP1A2	ENST00000361216.8 linkuse as main transcript	c.13-11_13-8del	splice_polypyrimidine_tract_variant, intron_variant	1	NM_000702.4	ENSP00000354490	P1
ATP1A2	ENST00000392233.7 linkuse as main transcript	c.13-11_13-8del	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000376066
ATP1A2	ENST00000472488.5 linkuse as main transcript	n.116-11_116-8del	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2
ATP1A2	ENST00000478587.1 linkuse as main transcript	n.112-11_112-8del	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110308

AN:

151896

Hom.:

42399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.846

Gnomad ASJ

AF:

0.837

Gnomad EAS

AF:

0.844

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.890

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.829

Gnomad OTH

AF:

0.761

GnomAD3 exomes

AF:

0.802

AC:

145273

AN:

181048

Hom.:

59341

AF XY:

0.800

AC XY:

77525

AN XY:

96942

show subpopulations

Gnomad AFR exome

AF:

0.443

Gnomad AMR exome

AF:

0.902

Gnomad ASJ exome

AF:

0.841

Gnomad EAS exome

AF:

0.843

Gnomad SAS exome

AF:

0.689

Gnomad FIN exome

AF:

0.887

Gnomad NFE exome

AF:

0.823

Gnomad OTH exome

AF:

0.821

GnomAD4 exome

AF:

0.814

AC:

1156790

AN:

1421862

Hom.:

474360

AF XY:

0.811

AC XY:

570564

AN XY:

703848

show subpopulations

Gnomad4 AFR exome

AF:

0.435

Gnomad4 AMR exome

AF:

0.897

Gnomad4 ASJ exome

AF:

0.844

Gnomad4 EAS exome

AF:

0.804

Gnomad4 SAS exome

AF:

0.693

Gnomad4 FIN exome

AF:

0.888

Gnomad4 NFE exome

AF:

0.828

Gnomad4 OTH exome

AF:

0.798

GnomAD4 genome

AF:

0.726

AC:

110354

AN:

152014

Hom.:

42415

Cov.:

AF XY:

0.730

AC XY:

54231

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.449

Gnomad4 AMR

AF:

0.846

Gnomad4 ASJ

AF:

0.837

Gnomad4 EAS

AF:

0.844

Gnomad4 SAS

AF:

0.677

Gnomad4 FIN

AF:

0.890

Gnomad4 NFE

AF:

0.829

Gnomad4 OTH

AF:

0.763

Alfa

AF:

0.781

Hom.:

7935

Bravo

AF:

0.720

Asia WGS

AF:

0.743

AC:

2585

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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 98% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 91. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2013	The variant is found in EPILEPSY panel(s). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 17, 2014	- -

Familial hemiplegic migraine

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Alternating hemiplegia of childhood

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Developmental and epileptic encephalopathy 98

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

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

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over