Submissions for variant NM_000017.4(ACADS):c.682_683del (p.Glu228fs)

dbSNP: rs786204691

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169499	SCV000220960	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2014-12-16	criteria provided, single submitter	literature only
GeneDx	RCV000185707	SCV000238628	pathogenic	not provided	2014-04-29	criteria provided, single submitter	clinical testing	The c.682_683delGA mutation in the ACADS gene has been reported previously in association with short chain acyl-CoA dehydrogenase deficiency (Pena et al., 2012). The deletion causes a frameshift starting with codon Glutamic Acid 228, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 16 of the new reading frame, denoted p.Glu228ArgfsX16. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The surrounding sequence GAAA{delGA}AGAC. The variant is found in ACADS panel(s).
Genome-Nilou Lab	RCV000169499	SCV002033279	pathogenic	Deficiency of butyryl-CoA dehydrogenase	2021-11-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000169499	SCV003442074	pathogenic	Deficiency of butyryl-CoA dehydrogenase	2023-01-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu228Argfs*16) in the ACADS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADS are known to be pathogenic (PMID: 12736383, 18523805). ClinVar contains an entry for this variant (Variation ID: 189093). This premature translational stop signal has been observed in individual(s) with clinical features of ACADS-related conditions (PMID: 22241096). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003965221	SCV004780356	likely pathogenic	ACADS-related disorder	2023-10-20	criteria provided, single submitter	clinical testing	The ACADS c.682_683delGA variant is predicted to result in a frameshift and premature protein termination (p.Glu228Argfs*16). This variant was reported along with another potentially causative variant in an individual with short-chain acyl-CoA-dehydrogenase deficiency (Pena. 2012. PubMed ID: 22241096). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in ACADS are expected to be pathogenic. This variant is interpreted as likely pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000185707	SCV005074770	pathogenic	not provided	2024-06-01	criteria provided, single submitter	clinical testing	ACADS: PVS1, PM2, PM3:Supporting