rs61734526
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_000702.4(ATP1A2):c.1125G>A(p.Lys375=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000551 in 1,614,194 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 0 hom. )
Consequence
ATP1A2
NM_000702.4 synonymous
NM_000702.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.94
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
Variant 1-160128759-G-A is Benign according to our data. Variant chr1-160128759-G-A is described in ClinVar as [Benign]. Clinvar id is 136447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00304 (463/152300) while in subpopulation AFR AF= 0.0105 (437/41562). AF 95% confidence interval is 0.0097. There are 2 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 463 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A2 | NM_000702.4 | c.1125G>A | p.Lys375= | synonymous_variant | 9/23 | ENST00000361216.8 | |
ATP1A2 | XM_047421286.1 | c.234G>A | p.Lys78= | synonymous_variant | 2/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A2 | ENST00000361216.8 | c.1125G>A | p.Lys375= | synonymous_variant | 9/23 | 1 | NM_000702.4 | P1 | |
ATP1A2 | ENST00000392233.7 | c.1125G>A | p.Lys375= | synonymous_variant | 9/23 | 5 | |||
ATP1A2 | ENST00000447527.1 | c.258G>A | p.Lys86= | synonymous_variant | 2/16 | 2 | |||
ATP1A2 | ENST00000472488.5 | n.1228G>A | non_coding_transcript_exon_variant | 9/20 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00304 AC: 462AN: 152182Hom.: 2 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
462
AN:
152182
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000815 AC: 205AN: 251474Hom.: 1 AF XY: 0.000589 AC XY: 80AN XY: 135910
GnomAD3 exomes
AF:
AC:
205
AN:
251474
Hom.:
AF XY:
AC XY:
80
AN XY:
135910
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000292 AC: 427AN: 1461894Hom.: 0 Cov.: 34 AF XY: 0.000267 AC XY: 194AN XY: 727248
GnomAD4 exome
AF:
AC:
427
AN:
1461894
Hom.:
Cov.:
34
AF XY:
AC XY:
194
AN XY:
727248
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00304 AC: 463AN: 152300Hom.: 2 Cov.: 32 AF XY: 0.00277 AC XY: 206AN XY: 74472
GnomAD4 genome
?
AF:
AC:
463
AN:
152300
Hom.:
Cov.:
32
AF XY:
AC XY:
206
AN XY:
74472
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
5
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 04, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 26, 2013 | 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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 21, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | ATP1A2: BP4, BS1, BS2 - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 29, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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 | - - |
ATP1A2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Familial hemiplegic migraine Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Alternating hemiplegia of childhood 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at