rs2854248

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000702.4(ATP1A2):c.495+81T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,578,876 control chromosomes in the GnomAD database, including 99,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12348 hom., cov: 32)

Exomes 𝑓: 0.35 ( 87187 hom. )

Consequence

ATP1A2
NM_000702.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-160124137-T-A is Benign according to our data. Variant chr1-160124137-T-A is described in ClinVar as [Benign]. Clinvar id is 670754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-160124137-T-A is described in Lovd as [Benign]. Variant chr1-160124137-T-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1A2	NM_000702.4 link	c.495+81T>A		intron_variant		ENST00000361216.8	NP_000693.1	P50993A0A0S2Z3W6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ATP1A2	ENST00000361216.8 link	c.495+81T>A	intron_variant	1	NM_000702.4	ENSP00000354490.3	P50993
ATP1A2	ENST00000392233.7 link	c.495+81T>A	intron_variant	5		ENSP00000376066.3	B1AKY9
ATP1A2	ENST00000468587.1 link	n.99+81T>A	intron_variant	2
ATP1A2	ENST00000472488.5 link	n.598+81T>A	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

60076

AN:

151954

Hom.:

12346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.404

GnomAD4 exome

AF:

0.346

AC:

493292

AN:

1426804

Hom.:

87187

Cov.:

AF XY:

0.342

AC XY:

243003

AN XY:

709690

show subpopulations

Gnomad4 AFR exome

AF:

0.483

Gnomad4 AMR exome

AF:

0.455

Gnomad4 ASJ exome

AF:

0.401

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.348

Gnomad4 NFE exome

AF:

0.338

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.395

AC:

60121

AN:

152072

Hom.:

12348

Cov.:

AF XY:

0.395

AC XY:

29356

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.466

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.345

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.373

Hom.:

1404

Bravo

AF:

0.414

Asia WGS

AF:

0.384

AC:

1334

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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 22% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 20. Only high quality variants are reported. -

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

- -

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

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.0

DANN

Benign

0.40

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