Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317335 | SCV004020604 | likely pathogenic | Bifunctional peroxisomal enzyme deficiency | 2023-06-12 | criteria provided, single submitter | clinical testing | Variant summary: HSD17B4 c.1210-11C>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 3' acceptor site. One predicts the variant creates a 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing resulting in exon 14 skipping, predicted to cause a frameshift resulting in premature termination of three amino acids downstream (p.Val404Glufs*3) (example: Werner_2022). The variant allele was found at a frequency of 1.2e-05 in 250824 control chromosomes. c.1210-11C>G has been reported in the literature in compound heterozygous individuals affected with D-Bifunctional Protein Deficiency (examples: Meng_2017, Werner_2022). The following publications have been ascertained in the context of this evaluation (PMID: 28973083, 34623748). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, classifying the variant as likely pathogenic (n=1), uncertain significance (n=1), or likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Baylor Genetics | RCV003317335 | SCV004192380 | likely pathogenic | Bifunctional peroxisomal enzyme deficiency | 2023-09-22 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000676080 | SCV000801816 | likely benign | not provided | 2016-10-14 | no assertion criteria provided | clinical testing | |
Eurofins Ntd Llc |
RCV000676080 | SCV000859249 | uncertain significance | not provided | 2018-01-22 | flagged submission | clinical testing | |
Elsea Laboratory, |
RCV001250119 | SCV001424305 | likely pathogenic | Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 1 | 2020-04-01 | no assertion criteria provided | clinical testing |