ClinVar Miner

Submissions for variant NM_000288.4(PEX7):c.653C>T (p.Ala218Val) (rs121909151)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000032925 SCV000776819 likely pathogenic Peroxisome biogenesis disorder 9B 2019-10-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 218 of the PEX7 protein (p.Ala218Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs121909151, ExAC 0.003%). This variant has been reported as homozygous or in combination with another PEX7 variant in several individuals affected with rhizomelic chondrodysplasia punctata (PMID: 9090381, 10083738, 12325024, 11781871). ClinVar contains an entry for this variant (Variation ID: 7781). Experimental studies have shown that this missense change reduces binding to both PTS2 and PEX5pL resulting in impairment of peroxisomal import of PTS2 (PMID: 11756410, 11781871). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV000008223 SCV001163001 pathogenic Rhizomelic chondrodysplasia punctata type 1 criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000008223 SCV001193850 likely pathogenic Rhizomelic chondrodysplasia punctata type 1 2019-12-09 criteria provided, single submitter clinical testing NM_000288.3(PEX7):c.653C>T(A218V) is classified as likely pathogenic in the context of rhizomelic chondrodysplasia punctata type 1. Sources cited for classification include the following: PMID 12325024, 9090382, 9090381 and 11756410. Classification of NM_000288.3(PEX7):c.653C>T(A218V) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000008223 SCV000028430 pathogenic Rhizomelic chondrodysplasia punctata type 1 1997-04-01 no assertion criteria provided literature only
GeneReviews RCV000008223 SCV000055660 pathologic Rhizomelic chondrodysplasia punctata type 1 2012-09-13 no assertion criteria provided curation Converted during submission to Pathogenic.
OMIM RCV000032925 SCV000056697 pathogenic Peroxisome biogenesis disorder 9B 1997-04-01 no assertion criteria provided literature only
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000656252 SCV000778213 pathogenic not provided 2016-08-26 no assertion criteria provided clinical testing

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