ClinVar Miner

Submissions for variant NM_000318.3(PEX2):c.339_345del (p.Gly113_Arg114insTer) (rs764771123)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726022 SCV000341287 pathogenic not provided 2016-04-11 criteria provided, single submitter clinical testing
Counsyl RCV000310327 SCV000487609 likely pathogenic Peroxisome biogenesis disorder 5a (zellweger) 2016-08-16 criteria provided, single submitter clinical testing
Counsyl RCV000410454 SCV000487610 likely pathogenic Peroxisome biogenesis disorder 5B 2016-08-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587540 SCV000696557 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2017-04-28 criteria provided, single submitter clinical testing Variant summary: The PEX2 c.339_345delCAGGTGG (p.Arg114fs) variant results in a premature termination codon, predicted to cause a truncated or absent PEX2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. LCA has classified another downstream truncation variant, c.355C>T (p.Arg119X) as pathogenic. This variant was found in 3/121458 control chromosomes at a frequency of 0.0000247, which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX2 variant (0.001118). A publication has cited the variant in two individuals, one homozygous and one assumed compound heterozygous, diagnosed with ZS (Ebberink_2010). In addition, multiple clinical diagnostic laboratories classified this variant as "likely pathogenic/pathogenic. Taken together, this variant is classified as "Pathogenic."
Invitae RCV000310327 SCV000963663 pathogenic Peroxisome biogenesis disorder 5a (zellweger) 2019-08-30 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PEX2 gene (p.Arg114*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 192 amino acids of the PEX2 protein. This variant is present in population databases (rs764771123, ExAC 0.004%). This variant has been observed in an individual affected with Zellweger syndrome (PMID: 21031596). ClinVar contains an entry for this variant (Variation ID: 287499). This variant disrupts the C-terminus of the PEX2 protein. Other variant(s) that disrupt this region (p.Arg119*) have been determined to be pathogenic (PMID: 10528859, 9585609, 9452066, 1546315). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197103 SCV001367739 pathogenic Epilepsy 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PS3,PM2,PP3. This variant was detected in heterozygous state.

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