13-25860860-A-G
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_016529.6(ATP8A2):āc.3075A>Gā(p.Lys1025=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00393 in 1,584,032 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0032 ( 0 hom., cov: 33)
Exomes š: 0.0040 ( 21 hom. )
Consequence
ATP8A2
NM_016529.6 splice_region, synonymous
NM_016529.6 splice_region, synonymous
Scores
2
Splicing: ADA: 0.00009621
2
Clinical Significance
Conservation
PhyloP100: 3.89
Genes affected
ATP8A2 (HGNC:13533): (ATPase phospholipid transporting 8A2) The protein encoded by this gene is a member of the P4 ATPase family of proteins, which are thought to be involved in a process called lipid flipping, whereby phospholipids are translocated inwards from the exoplasmic leaflet to the cytosolic leaflet of the cell membrane, which aids in generating and maintaining asymmetry in membrane lipids. This protein is predicted to contain an E1 E2 ATPase, a haloacid dehalogenase-like hydrolase (HAD) domain, and multiple transmembrane domains. Associations between this protein and cell cycle control protein 50A are important for translocation of phosphatidylserine across membranes. Mutations in this gene have been associated with a syndrome (CAMRQ4) characterized by cerebellar ataxia and cognitive disabilities. In addition, a translocation breakpoint within this gene was observed in an individual with neurological dysfunction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]
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=-0.48).
BP6
Variant 13-25860860-A-G is Benign according to our data. Variant chr13-25860860-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 218739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00318 (484/152318) while in subpopulation NFE AF= 0.00544 (370/68034). AF 95% confidence interval is 0.00498. There are 0 homozygotes in gnomad4. There are 225 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP8A2 | NM_016529.6 | c.3075A>G | p.Lys1025= | splice_region_variant, synonymous_variant | 32/37 | ENST00000381655.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP8A2 | ENST00000381655.7 | c.3075A>G | p.Lys1025= | splice_region_variant, synonymous_variant | 32/37 | 1 | NM_016529.6 |
Frequencies
GnomAD3 genomes AF: 0.00318 AC: 484AN: 152200Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
484
AN:
152200
Hom.:
Cov.:
33
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: 0.00304 AC: 660AN: 216988Hom.: 3 AF XY: 0.00312 AC XY: 364AN XY: 116742
GnomAD3 exomes
AF:
AC:
660
AN:
216988
Hom.:
AF XY:
AC XY:
364
AN XY:
116742
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: 0.00401 AC: 5745AN: 1431714Hom.: 21 Cov.: 27 AF XY: 0.00402 AC XY: 2858AN XY: 710880
GnomAD4 exome
AF:
AC:
5745
AN:
1431714
Hom.:
Cov.:
27
AF XY:
AC XY:
2858
AN XY:
710880
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: 0.00318 AC: 484AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.00302 AC XY: 225AN XY: 74478
GnomAD4 genome
AF:
AC:
484
AN:
152318
Hom.:
Cov.:
33
AF XY:
AC XY:
225
AN XY:
74478
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:
3
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 09, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | ATP8A2: BP4, BP7, BS2 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jul 17, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 01, 2017 | 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at