ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.936_937del (p.His312_Thr313insTer)

dbSNP: rs758055753
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599590 SCV000710327 likely pathogenic not provided 2022-10-05 criteria provided, single submitter clinical testing Observed with another HSD17B4 variant on the opposite allele (in trans) in a critically ill infant, however additional phenotypic information was not provided (Meng et al., 2017); Has been observed with a maternally inherited missense variant in this gene in a child with regression, ataxia and leukodystrophy; however paternal sample was not tested to be able to confirm phase (Farkas et al., 2019); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28973083, 30396834)
Baylor Genetics RCV000984186 SCV001162971 pathogenic Bifunctional peroxisomal enzyme deficiency criteria provided, single submitter clinical testing
Elsea Laboratory, Baylor College of Medicine RCV001250093 SCV001424280 pathogenic Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 1 2020-04-01 criteria provided, single submitter clinical testing
Invitae RCV001387755 SCV001588468 pathogenic Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2023-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr313*) in the HSD17B4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HSD17B4 are known to be pathogenic (PMID: 11810648, 16385454, 20673864). This variant is present in population databases (rs758055753, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with clinical features of D-bifunctional protein deficiency (PMID: 28973083, 30396834). ClinVar contains an entry for this variant (Variation ID: 504023). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003411447 SCV004116047 pathogenic HSD17B4-related condition 2024-02-23 criteria provided, single submitter clinical testing The HSD17B4 c.936_937delTA variant is predicted to result in premature protein termination (p.Thr313*). This variant has been reported by whole exome sequencing in a critically ill infant, although no phenotypic details were provided (Meng et al. 2017. PubMed ID: 28973083) as well as in a patient with D-bifunctional protein deficiency (Farkas et al. 2018. PubMed ID: 30396834). This variant is reported in 0.036% of alleles in individuals of African descent in gnomAD. Nonsense variants in HSD17B4 are expected to be pathogenic. This variant is interpreted as pathogenic.
Counsyl RCV000984186 SCV001132226 likely pathogenic Bifunctional peroxisomal enzyme deficiency 2014-11-04 no assertion criteria provided clinical testing
Natera, Inc. RCV000984186 SCV001458665 likely pathogenic Bifunctional peroxisomal enzyme deficiency 2020-09-16 no assertion criteria provided clinical testing

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