rs66716803
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_004320.6(ATP2A1):c.1764+6del 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 0.0184 in 1,612,294 control chromosomes in the GnomAD database, including 1,955 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.064 ( 849 hom., cov: 31)
Exomes 𝑓: 0.014 ( 1106 hom. )
Consequence
ATP2A1
NM_004320.6 splice_donor_region, intron
NM_004320.6 splice_donor_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.108
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 -16 ACMG points.
BP6
?
Variant 16-28898456-GC-G is Benign according to our data. Variant chr16-28898456-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 96541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2A1 | NM_004320.6 | c.1764+6del | splice_donor_region_variant, intron_variant | ENST00000395503.9 | |||
ATP2A1 | NM_001286075.2 | c.1389+6del | splice_donor_region_variant, intron_variant | ||||
ATP2A1 | NM_173201.5 | c.1764+6del | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2A1 | ENST00000395503.9 | c.1764+6del | splice_donor_region_variant, intron_variant | 1 | NM_004320.6 | P4 | |||
ATP2A1 | ENST00000357084.7 | c.1764+6del | splice_donor_region_variant, intron_variant | 2 | A1 | ||||
ATP2A1 | ENST00000536376.5 | c.1389+6del | splice_donor_region_variant, intron_variant | 2 | |||||
ATP2A1 | ENST00000564732.1 | c.*407+6del | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0637 AC: 9692AN: 152158Hom.: 848 Cov.: 31
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GnomAD3 exomes AF: 0.0312 AC: 7554AN: 242494Hom.: 512 AF XY: 0.0258 AC XY: 3413AN XY: 132148
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GnomAD4 exome AF: 0.0137 AC: 19997AN: 1460018Hom.: 1106 Cov.: 31 AF XY: 0.0128 AC XY: 9302AN XY: 726260
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GnomAD4 genome ? AF: 0.0638 AC: 9711AN: 152276Hom.: 849 Cov.: 31 AF XY: 0.0622 AC XY: 4629AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Brody myopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 15, 2013 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 22, 2018 | - - |
Computational scores
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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