rs376128790
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_000702.4(ATP1A2):c.1578G>A(p.Pro526Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,176 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
ATP1A2
NM_000702.4 synonymous
NM_000702.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.00
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 1-160130218-G-A is Benign according to our data. Variant chr1-160130218-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 387509.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-2 with no splicing effect.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP1A2 | NM_000702.4 | c.1578G>A | p.Pro526Pro | synonymous_variant | 12/23 | ENST00000361216.8 | NP_000693.1 | |
ATP1A2 | XM_047421286.1 | c.687G>A | p.Pro229Pro | synonymous_variant | 5/16 | XP_047277242.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP1A2 | ENST00000361216.8 | c.1578G>A | p.Pro526Pro | synonymous_variant | 12/23 | 1 | NM_000702.4 | ENSP00000354490.3 | ||
ATP1A2 | ENST00000392233.7 | c.1578G>A | p.Pro526Pro | synonymous_variant | 12/23 | 5 | ENSP00000376066.3 | |||
ATP1A2 | ENST00000447527.1 | c.708G>A | p.Pro236Pro | synonymous_variant | 5/16 | 2 | ENSP00000411705.1 | |||
ATP1A2 | ENST00000472488.5 | n.1681G>A | non_coding_transcript_exon_variant | 12/20 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
5
AN:
152168
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: 0.0000358 AC: 9AN: 251438Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135906
GnomAD3 exomes
AF:
AC:
9
AN:
251438
Hom.:
AF XY:
AC XY:
6
AN XY:
135906
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: 0.0000664 AC: 97AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 49AN XY: 727246
GnomAD4 exome
AF:
AC:
97
AN:
1461890
Hom.:
Cov.:
32
AF XY:
AC XY:
49
AN XY:
727246
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: 0.0000328 AC: 5AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74452
GnomAD4 genome
AF:
AC:
5
AN:
152286
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74452
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:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Migraine, familial hemiplegic, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 27, 2021 | - - |
Familial hemiplegic migraine Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Alternating hemiplegia of childhood 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
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