rs2071341
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_004320.6(ATP2A1):c.2524+3G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,613,700 control chromosomes in the GnomAD database, including 2,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 154 hom., cov: 32)
Exomes 𝑓: 0.020 ( 1955 hom. )
Consequence
ATP2A1
NM_004320.6 splice_donor_region, intron
NM_004320.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9975
1
1
Clinical Significance
Conservation
PhyloP100: 0.805
Genes affected
ATP2A1 (HGNC:811): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 16-28902389-G-T is Benign according to our data. Variant chr16-28902389-G-T is described in ClinVar as [Benign]. Clinvar id is 318787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-28902389-G-T is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2A1 | NM_004320.6 | c.2524+3G>T | splice_donor_region_variant, intron_variant | ENST00000395503.9 | |||
ATP2A1 | NM_001286075.2 | c.2149+3G>T | splice_donor_region_variant, intron_variant | ||||
ATP2A1 | NM_173201.5 | c.2524+3G>T | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2A1 | ENST00000395503.9 | c.2524+3G>T | splice_donor_region_variant, intron_variant | 1 | NM_004320.6 | P4 | |||
ATP2A1 | ENST00000357084.7 | c.2524+3G>T | splice_donor_region_variant, intron_variant | 2 | A1 | ||||
ATP2A1 | ENST00000536376.5 | c.2149+3G>T | splice_donor_region_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0215 AC: 3275AN: 152046Hom.: 155 Cov.: 32
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GnomAD3 exomes AF: 0.0492 AC: 12313AN: 250240Hom.: 936 AF XY: 0.0463 AC XY: 6273AN XY: 135444
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GnomAD4 exome AF: 0.0201 AC: 29433AN: 1461536Hom.: 1955 Cov.: 33 AF XY: 0.0213 AC XY: 15490AN XY: 727026
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GnomAD4 genome ? AF: 0.0215 AC: 3278AN: 152164Hom.: 154 Cov.: 32 AF XY: 0.0243 AC XY: 1810AN XY: 74372
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Brody myopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 12, 2016 | 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:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 01, 2019 | - - |
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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dbscSNV1_ADA
Pathogenic
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