ClinVar Miner

Submissions for variant NM_001609.3(ACADSB):c.303+1G>A (rs147936696)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498442 SCV000589304 pathogenic not provided 2018-11-21 criteria provided, single submitter clinical testing The c.303+1 G>A splice site variant in the ACADSB gene has been previously reported in two patients with short / branched chain acyl-CoA dehydrogenase (SBCAD) deficiency who are homozygous for c.303+1 G>A (Alfardan et al. 2010). One patient was detected by newborn screening and is reported to be asymptomatic, while the other patient presented at 4 years of age with developmental delay, simplified brain sulci pattern and microcephaly (Alfardan et al. 2010). This variant destroys the canonical splice donor site in intron 3, and is expected to cause abnormal gene splicing. Therefore, this variant is considered to be pathogenic.
Invitae RCV000185535 SCV000830358 pathogenic Deficiency of 2-methylbutyryl-CoA dehydrogenase 2017-10-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the ACADSB gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs147936696, ExAC 0.05%). This variant has been reported in the homozygous state in individuals affected with short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency (PMID: 20547083). This variant is also known as IVS3+1G>A. ClinVar contains an entry for this variant (Variation ID: 203367). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ACADSB are known to be pathogenic (PMID: 20547083). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000498442 SCV000854866 likely pathogenic not provided 2017-08-29 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000185535 SCV000915460 likely pathogenic Deficiency of 2-methylbutyryl-CoA dehydrogenase 2018-12-03 criteria provided, single submitter clinical testing The ACADSB c.303+1G>A variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. The c.303+1G>A variant has been reported in one study in which it was found in a homozygous state in two individuals with acyl-CoA dehydrogenase deficiency, oneof whom was symptomatic and the other asymptomatic newborn (Alfardan et al. 2010). Control data are unavailable for this variant, which is reported at a frequency of 0.000931 in the European American population of the Exome Sequencing Project. Based on the potential impact of splice donor variants and the clinical evidence, the c.303+1G>A variant is classified as likely pathogenic for acyl-CoA dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000498442 SCV001148113 uncertain significance not provided 2018-08-01 criteria provided, single submitter clinical testing
Division of Human Genetics,Children's Hospital of Philadelphia RCV000185535 SCV000238410 pathogenic Deficiency of 2-methylbutyryl-CoA dehydrogenase 2014-07-17 no assertion criteria provided research This patient is a carrier of a heterozygous pathogenic variant in the ACADSB gene associated with 2-methylbutyrylglycinuria. The ACADSB variant (c.303+1G>A) identified in this patient is located in the first intronic position of the donor splice site and, therefore, meets the criteria for a pathogenic variant.

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