ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.2770G>T (p.Ala924Ser) (rs34551839)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224155 SCV000281450 likely benign not provided 2015-10-28 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV001083504 SCV001115115 benign Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001161844 SCV001323751 benign Peroxisome biogenesis disorder 4a (zellweger) 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Integrated Genetics/Laboratory Corporation of America RCV001201315 SCV001372457 benign not specified 2020-06-26 criteria provided, single submitter clinical testing Variant summary: PEX6 c.2770G>T (p.Ala924Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 251220 control chromosomes, predominantly at a frequency of 0.02 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 10 fold of the estimated maximal expected allele frequency for a pathogenic variant in PEX6 causing Zellweger Syndrome phenotype (0.0019), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.2770G>T in individuals affected with Zellweger Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=2)/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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