1-160129051-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4BP6_ModerateBS2
The NM_000702.4(ATP1A2):c.1288G>A(p.Val430Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,124 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
ATP1A2
NM_000702.4 missense
NM_000702.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 7.85
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 Likely_benign. Variant got -6 ACMG points.
PP2
Missense variant where missense usually causes diseases, ATP1A2
BP4
Computational evidence support a benign effect (MetaRNN=0.26448777).
BP6
Variant 1-160129051-G-A is Benign according to our data. Variant chr1-160129051-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 583212.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A2 | NM_000702.4 | c.1288G>A | p.Val430Ile | missense_variant | 10/23 | ENST00000361216.8 | |
ATP1A2 | XM_047421286.1 | c.397G>A | p.Val133Ile | missense_variant | 3/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A2 | ENST00000361216.8 | c.1288G>A | p.Val430Ile | missense_variant | 10/23 | 1 | NM_000702.4 | P1 | |
ATP1A2 | ENST00000392233.7 | c.1288G>A | p.Val430Ile | missense_variant | 10/23 | 5 | |||
ATP1A2 | ENST00000447527.1 | c.421G>A | p.Val141Ile | missense_variant | 3/16 | 2 | |||
ATP1A2 | ENST00000472488.5 | n.1391G>A | non_coding_transcript_exon_variant | 10/20 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248882Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134488
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460814Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 726570
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial hemiplegic migraine Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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