ClinVar Miner

Submissions for variant NM_016042.4(EXOSC3):c.395A>C (p.Asp132Ala) (rs141138948)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000190687 SCV000244128 pathogenic Inborn genetic diseases 2014-06-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Baylor Miraca Genetics Laboratories, RCV000024366 SCV000807246 pathogenic Pontocerebellar hypoplasia, type 1b 2017-09-01 criteria provided, single submitter clinical testing This mutation has been previously reported as disease-causing and was found once in our laboratory homozygous in a 7-year-old male with severe intellectual disability, hypotonia, progressive dystonia, dysmorphism, microcephaly, progressive contractures, failure to thrive, and a similarly affected sibling
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224817 SCV000281509 pathogenic not provided 2014-06-18 criteria provided, single submitter clinical testing
Clinical Genetics,University of Leipzig RCV000024366 SCV000886743 pathogenic Pontocerebellar hypoplasia, type 1b 2019-03-07 criteria provided, single submitter clinical testing
Division of Human Genetics,Children's Hospital of Philadelphia RCV000024366 SCV000536754 pathogenic Pontocerebellar hypoplasia, type 1b 2016-04-05 no assertion criteria provided research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000224817 SCV000706778 pathogenic not provided 2017-03-08 criteria provided, single submitter clinical testing
Fulgent Genetics RCV000024366 SCV000611264 pathogenic Pontocerebellar hypoplasia, type 1b 2017-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000224817 SCV000321607 pathogenic not provided 2017-04-12 criteria provided, single submitter clinical testing The D132A variant in the EXOSC3 gene has been reported previously in both the homozygous and compound heterozygous state in multiple unrelated individuals with pontocerebellar hypoplasia type 1 (PCH1) (Wan et al., 2012). The D132A variant has also been reported in the homozygous state in multiple individuals with symptoms of variable severity including hypotonia, developmental delay, spinal anterior horn involvement, cerebellar hypoplasia with preservation of the pons, and prolonged survival into the second decade, whereas the presence of the D132A variant in the compound heterozygous state with a second more severe pathogenic variant led to a progressive clinical course and infant death in some affected individuals (Biancheri et al., 2013; Eggens et al., 2014). The D132A variant is observed in 34/66726 (0.05%) alleles from individuals of non-Finnish European background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The D132A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D132A as a pathogenic variant.
GeneReviews RCV000024366 SCV000189382 pathogenic Pontocerebellar hypoplasia, type 1b 2014-04-22 no assertion criteria provided literature only
Genetic Services Laboratory, University of Chicago RCV000024366 SCV000247328 likely pathogenic Pontocerebellar hypoplasia, type 1b 2015-05-22 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000024366 SCV000746484 pathogenic Pontocerebellar hypoplasia, type 1b 2017-12-03 criteria provided, single submitter clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center RCV000761613 SCV000891780 pathogenic Neurodevelopmental delay 2016-04-12 criteria provided, single submitter clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center RCV000761614 SCV000891781 pathogenic Muscular hypotonia 2016-09-04 criteria provided, single submitter clinical testing
OMIM RCV000024366 SCV000045659 pathogenic Pontocerebellar hypoplasia, type 1b 2013-11-01 no assertion criteria provided literature only

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