Submissions for variant NM_000288.4(PEX7):c.870_871insCAA (p.Cys290_Gly291insGln)

dbSNP: rs267608257

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV001004182	SCV001163003	likely pathogenic	Rhizomelic chondrodysplasia punctata type 1		criteria provided, single submitter	clinical testing
Invitae	RCV001860551	SCV002119765	uncertain significance	Peroxisome biogenesis disorder 9B	2021-11-11	criteria provided, single submitter	clinical testing	This variant, c.870_871insCAA, results in the insertion of 1 amino acid(s) of the PEX7 protein (p.Cys290_Gly291insGln), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with rhizomelic chondrodysplasia punctata (PMID: 12325024). This variant is also known as c.871_873insCAAp.Q291ins. ClinVar contains an entry for this variant (Variation ID: 813368). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002236071	SCV002511468	uncertain significance	not specified	2024-03-10	criteria provided, single submitter	clinical testing	Variant summary: PEX7 c.870_871insCAA (p.Cys290_Gly291insGln) results in an in-frame insertion that is predicted to insert one amino acid into the encoded protein. The variant was absent in 251294 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.870_871insCAA has been reported in the literature as a compound heterozygous genotype in at-least one individual affected with Rhizomelic Chondrodysplasia Punctata Type 1 (example, Braverman_2002). This report does not provide unequivocal conclusions about association of the variant with Rhizomelic Chondrodysplasia Punctata Type 1. At least one publication reports experimental evidence demonstrating impaired PTS2 protein import due to exclusively cytosolic localization in RCDP cells (Braverman_2002). The following publication has been ascertained in the context of this evaluation (PMID: 12325024). ClinVar contains an entry for this variant (Variation ID: 813368). Based on the evidence outlined above, the variant was classified as uncertain significance.
Baylor Genetics	RCV001860551	SCV004203921	likely pathogenic	Peroxisome biogenesis disorder 9B	2022-01-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004545012	SCV004800070	uncertain significance	PEX7-related disorder	2023-11-28	criteria provided, single submitter	clinical testing	The PEX7 c.870_871insCAA variant is predicted to result in an in-frame amino acid insertion (p.Cys290_Gly291insGln). This variant (also referred to as Q290ins within the literature) was reported in a compound heterozygous individual presenting with Rhizomelic chondrodysplasia punctata (Table 3, Braverman et al 2002. PubMed ID: 12325024). This variant has not been reported in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.