Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000542072 | SCV004009589 | uncertain significance | Glycogen storage disease, type II | 2023-06-20 | reviewed by expert panel | curation | The NM_000152.5: c.2417C>T variant in GAA is a missense variant predicted to cause substitution of threonine by methionine at amino acid 806 (p.Thr806Met). To our knowledge, this variant has not been reported in the literature in individuals with Pompe disease, and the results of experimental studies are not available. The highest population minor allele frequency in gnomAD v2.1.1 is 0.001189 (42/35310 alleles) in Latino/Admixed American population. This allele frequency meets neither the PM2 allele frequency threshold (<0.001) nor the BS1 allele frequency threshold (>0.005) specified by the ClinGen Lysosomal Diseases VCEP. The computational predictor REVEL gives a score of 0.435 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAA function. No impact on splicing is predicted by SpliceAI (BP4). There is a ClinVar entry for this variant (Variation ID: 252467). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for Pompe disease due to insufficient evidence. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): BP4. (Classification approved by the ClinGen Lysosomal Diseases VCEP on June 20, 2023). |
Genomic Diagnostic Laboratory, |
RCV000238987 | SCV000296876 | uncertain significance | not specified | 2015-10-16 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000725668 | SCV000338490 | uncertain significance | not provided | 2016-01-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000542072 | SCV000626569 | likely benign | Glycogen storage disease, type II | 2024-01-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000725668 | SCV001502250 | likely benign | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000725668 | SCV001767605 | uncertain significance | not provided | 2022-12-29 | criteria provided, single submitter | clinical testing | Reported previously as part of a thesis project of genetic variation identified among healthy Armenian individuals through exome sequencing (Akopyan, 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22253258, 19343043) |
Genome- |
RCV000542072 | SCV001810193 | uncertain significance | Glycogen storage disease, type II | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002519855 | SCV003691858 | uncertain significance | Inborn genetic diseases | 2022-04-07 | criteria provided, single submitter | clinical testing | The c.2417C>T (p.T806M) alteration is located in exon 17 (coding exon 16) of the GAA gene. This alteration results from a C to T substitution at nucleotide position 2417, causing the threonine (T) at amino acid position 806 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV000725668 | SCV003816202 | uncertain significance | not provided | 2021-08-05 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000542072 | SCV001455441 | uncertain significance | Glycogen storage disease, type II | 2020-01-17 | no assertion criteria provided | clinical testing |