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

dbSNP: rs758055753

Total submissions: 7

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	2024-02-25	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
Labcorp Genetics (formerly Invitae), Labcorp	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.
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
PreventionGenetics, part of Exact Sciences	RCV004530729	SCV004116047	pathogenic	HSD17B4-related disorder	2024-02-23	no assertion criteria provided	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.