rs373796693

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000702.4(ATP1A2):c.13-11_13-8delTCCT variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.88

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

hemiplegic migraine-developmental and epileptic encephalopathy spectrum
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
migraine, familial hemiplegic, 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
alternating hemiplegia of childhood 1
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
developmental and epileptic encephalopathy 98
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
alternating hemiplegia of childhood
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial or sporadic hemiplegic migraine
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ATP1A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 rank	MANE	Protein	UniProt
ATP1A2	NM_000702.4 link	c.13-11_13-8delTCCT		splice_region_variant, intron_variant	Intron 1 of 22	ENST00000361216.8	NP_000693.1	P50993A0A0S2Z3W6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP1A2	ENST00000361216.8 link	c.13-14_13-11delCCTT	intron_variant	Intron 1 of 22	1	NM_000702.4	ENSP00000354490.3	P50993
ATP1A2	ENST00000392233.7 link	c.13-14_13-11delCCTT	intron_variant	Intron 1 of 22	5		ENSP00000376066.3	B1AKY9
ATP1A2	ENST00000472488.5 link	n.116-14_116-11delCCTT	intron_variant	Intron 1 of 19	2
ATP1A2	ENST00000478587.1 link	n.112-14_112-11delCCTT	intron_variant	Intron 1 of 1	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

GnomAD2 exomes

AF:

0.802

AC:

145273

AN:

181048

AF XY:

0.800

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 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

African (AFR)

AF:

0.435

AC:

14063

AN:

32312

American (AMR)

AF:

0.897

AC:

34245

AN:

38156

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

21495

AN:

25482

East Asian (EAS)

AF:

0.804

AC:

29709

AN:

36940

South Asian (SAS)

AF:

0.693

AC:

56382

AN:

81388

European-Finnish (FIN)

AF:

0.888

AC:

44998

AN:

50686

Middle Eastern (MID)

AF:

0.750

AC:

4232

AN:

5644

European-Non Finnish (NFE)

AF:

0.828

AC:

904614

AN:

1092322

Other (OTH)

AF:

0.798

AC:

47052

AN:

58932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10028

20056

30084

40112

50140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20662

41324

61986

82648

103310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.726

AC:

110354

AN:

152014

Hom.:

42415

Cov.:

AF XY:

0.730

AC XY:

54231

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.449

AC:

18628

AN:

41442

American (AMR)

AF:

0.846

AC:

12923

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.837

AC:

2906

AN:

3470

East Asian (EAS)

AF:

0.844

AC:

4355

AN:

5158

South Asian (SAS)

AF:

0.677

AC:

3269

AN:

4832

European-Finnish (FIN)

AF:

0.890

AC:

9412

AN:

10580

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.829

AC:

56318

AN:

67946

Other (OTH)

AF:

0.763

AC:

1610

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1313

2625

3938

5250

6563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Mar 17, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jun 13, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The variant is found in EPILEPSY panel(s). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial hemiplegic migraine

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Alternating hemiplegia of childhood

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy 98

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Migraine, familial hemiplegic, 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Alternating hemiplegia of childhood 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over