rs111405592
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000702.4(ATP1A2):c.1470C>T(p.Ile490=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000867 in 1,614,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
ATP1A2
NM_000702.4 synonymous
NM_000702.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.25
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
?
Variant 1-160130110-C-T is Benign according to our data. Variant chr1-160130110-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 377529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.25 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00044 (67/152308) while in subpopulation AFR AF= 0.00156 (65/41560). AF 95% confidence interval is 0.00126. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 67 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A2 | NM_000702.4 | c.1470C>T | p.Ile490= | synonymous_variant | 12/23 | ENST00000361216.8 | |
ATP1A2 | XM_047421286.1 | c.579C>T | p.Ile193= | synonymous_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A2 | ENST00000361216.8 | c.1470C>T | p.Ile490= | synonymous_variant | 12/23 | 1 | NM_000702.4 | P1 | |
ATP1A2 | ENST00000392233.7 | c.1470C>T | p.Ile490= | synonymous_variant | 12/23 | 5 | |||
ATP1A2 | ENST00000447527.1 | c.603C>T | p.Ile201= | synonymous_variant | 5/16 | 2 | |||
ATP1A2 | ENST00000472488.5 | n.1573C>T | non_coding_transcript_exon_variant | 12/20 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000421 AC: 64AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000104 AC: 26AN: 251128Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135842
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GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727240
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GnomAD4 genome ? AF: 0.000440 AC: 67AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2015 | 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2017 | This alteration is classified as likely 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
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 12, 2019 | This variant is classified as likely 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 | Nov 28, 2023 | - - |
Alternating hemiplegia of childhood 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at