Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000338649 | SCV000444361 | likely benign | Triglyceride storage disease with ichthyosis | 2018-01-13 | criteria provided, single submitter | clinical testing | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| Invitae | RCV000907603 | SCV001052319 | likely benign | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000907603 | SCV002496809 | likely benign | not provided | 2024-01-01 | criteria provided, single submitter | clinical testing | ABHD5: BP4 |
| Prevention |
RCV003972456 | SCV004790519 | likely benign | ABHD5-related condition | 2020-06-29 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
| Department of Pathology and Laboratory Medicine, |
RCV000907603 | SCV001552326 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The ABHD5 p.Asp9Gly variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs144420157) and in ClinVar (variant is classified as a VUS by Illumina for triglyceride storage disease with ichthyosis). The variant was also identified in control databases in 168 of 228570 chromosomes at a frequency of 0.000735 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 102 of 26300 chromosomes (freq: 0.003878), Other in 7 of 5612 chromosomes (freq: 0.001247), European (non-Finnish) in 55 of 104330 chromosomes (freq: 0.000527), Ashkenazi Jewish in 1 of 8798 chromosomes (freq: 0.000114), East Asian in 1 of 13384 chromosomes (freq: 0.000075), African in 1 of 18420 chromosomes (freq: 0.000054) and Latino in 1 of 29324 chromosomes (freq: 0.000034); it was not observed in the European (Finnish) population. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, GeneSplicer) predict a greater than 10% difference in splicing. The p.Asp9 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |