ClinVar Miner

Submissions for variant NM_000288.4(PEX7):c.340-10A>G (rs267608255)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000032116 SCV000460534 uncertain significance Phytanic acid storage disease 2016-06-14 criteria provided, single submitter clinical testing The c.340-10A>G variant has been reported in one study by Braverman et al. (2002) in which it was found in a compound heterozygous state in two unrelated individuals with rhizomelic chondrodysplasia punctata, one with a splice site variant and one with a stop-gained variant as the second allele. The c.340-10A>G variant was absent from at least 100 control chromosomes but is reported at a frequency of 0.00019 in the European (Non-Finnish) population of the Exome Aggregation Consortium. RT-PCR studies demonstrated that the c.340-10A>G variant produced lower levels of mRNA compared to wildtype, which is consistent with the milder disease phenotype in the patients. Based on the available evidence, the c.340-10A>G variant is classified as a variant of unknown significance but suspicious for pathogenicity for rhizomelic chondrodysplasia punctata.
Illumina Clinical Services Laboratory,Illumina RCV000393497 SCV000460535 uncertain significance Rhizomelic chondrodysplasia punctata type 1 2017-04-28 criteria provided, single submitter clinical testing The PEX7 c.340-10A>G variant is an intron variant that has been reported in one study by Braverman et al. (2002), in which it was found in a compound heterozygous state in two unrelated individuals with rhizomelic chondrodysplasia punctata. One of these individuals had a splice site variant as the second allele, and one had a stop-gained variant. The c.340-10A>G variant was absent from at least 100 control chromosomes and is reported at a frequency of 0.00019 in the European (non-Finnish) population of the Exome Aggregation Consortium. RT-PCR studies demonstrated that the c.340-10A>G variant produced lower levels of mRNA compared to wildtype, which is consistent with the milder disease phenotype in the patients. Based on the available evidence, the c.340-10A>G variant is considered to be a variant of unknown significance but suspicious for pathogenicity for rhizomelic chondrodysplasia punctata. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000731239 SCV000859032 likely pathogenic not provided 2017-12-29 criteria provided, single submitter clinical testing
Invitae RCV000008229 SCV001227539 likely pathogenic Peroxisome biogenesis disorder 9B 2019-12-18 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the PEX7 gene. It does not directly change the encoded amino acid sequence of the PEX7 protein. This variant is present in population databases (rs267608255, ExAC 0.02%). This variant has been observed in individual(s) with rhizomelic chondrodysplasia punctata (PMID: 12325024). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS3-10A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 7787). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 12325024). 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.
OMIM RCV000008229 SCV000028436 pathogenic Peroxisome biogenesis disorder 9B 2002-10-01 no assertion criteria provided literature only
GeneReviews RCV000032116 SCV000055656 pathologic Phytanic acid storage disease 2012-09-13 no assertion criteria provided curation Converted during submission to Pathogenic.

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