Submissions for variant NM_000018.4(ACADVL):c.128G>A (p.Gly43Asp)

gnomAD frequency: 0.02763  dbSNP: rs2230178

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen	RCV000020071	SCV002576790	benign	Very long chain acyl-CoA dehydrogenase deficiency	2022-09-22	reviewed by expert panel	curation	The c.128G>A variant in ACADVL is well characterized as a benign polymorphism, being present in several VLCAD cases with alternate pathogenic variants (BP2; PMIDs: 11914034, 15210884, more in literature). The highest population minor allele frequency in gnomAD v2.1.1 is 0.17 in the East Asian population, which is higher than the ClinGen ACADVL Variant Curation Expert Panel threshold (≥0.007) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.259, which is below the threshold of 0.5, evidence that does not predict a damaging effect on ACADVL function (BP4). In summary, this variant meets criteria to be classified as benign for very long chain acyl-CoA dehydrogenase deficiency in an autosomal recessive manner. ACADVL-specific ACMG/AMP criteria applied: BA1; BP2; BP4
PreventionGenetics, part of Exact Sciences	RCV000253810	SCV000301514	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000253810	SCV000330910	benign	not specified	2015-08-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000020071	SCV000406306	benign	Very long chain acyl-CoA dehydrogenase deficiency	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000020071	SCV000654925	benign	Very long chain acyl-CoA dehydrogenase deficiency	2024-02-01	criteria provided, single submitter	clinical testing
Phosphorus, Inc.	RCV000020071	SCV000679760	benign	Very long chain acyl-CoA dehydrogenase deficiency	2017-08-01	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000020071	SCV001365173	benign	Very long chain acyl-CoA dehydrogenase deficiency	2019-11-01	criteria provided, single submitter	clinical testing	The NM_000018.3:c.128G>A (NP_000009.1:p.Gly43Asp) [GRCH38: NC_000017.11:g.7220187G>A] variant in ACADVL gene is interpretated to be Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: BS1, BS2
GeneDx	RCV001689571	SCV001910492	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000020071	SCV002049628	benign	Very long chain acyl-CoA dehydrogenase deficiency	2023-11-28	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000020071	SCV001455119	benign	Very long chain acyl-CoA dehydrogenase deficiency	2020-09-16	no assertion criteria provided	clinical testing