ClinVar Miner

Submissions for variant NM_145207.2(SPATA5):c.983_985delCAA (p.Thr330del) (rs796052243)

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Total submissions: 6
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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 RCV000190122 SCV000609648 likely pathogenic not provided 2017-05-01 criteria provided, single submitter clinical testing
GeneDx RCV000190122 SCV000710049 pathogenic not provided 2017-09-20 criteria provided, single submitter clinical testing The c.989_991delCAA variant in the SPATA5 gene has been reported previously in the homozygous and compound heterozygous state in multiple unrelated individuals with SPATA5-related disorders, including isolated sensorineural hearing loss (Tanaka et al., 2015; Szczaluba et al., 2017; Kurata et al., 2016). The c.989_991delCAA variant results in an in-frame deletion and is predicted to cause loss of a Threonine residue at codon 330, denoted p.Thr330del. The c.989_991delCAA variant is observed in one homozygous individual and in 15/66074 (0.02%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret c.989_991delCAA as a pathogenic variant.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000190122 SCV000240215 likely pathogenic not provided 2015-08-03 no assertion criteria provided clinical testing The p.T330del variant in the SPATA5 gene was found in the homozygous state and has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. The p.T330del variant results in the deletion of a single Threonine residue, denoted p.Thr330del, at a position that is conserved across species. The p.T330del variant was observed at an allele frequency of 0.0002 in approximately 33.000 individuals of European ancestry (ExAC database), indicating it is not a common benign variant in this population. However, in this database the variant is also present once in the homozygous state. Based on these data and because of highly similar clinical features between this patient and others with SPATA5 mutations we interpret the p.T330del variant as likely pathogenic.
Institute of Human Genetics,Klinikum rechts der Isar RCV000578291 SCV000680392 likely pathogenic Epilepsy, hearing loss, and mental retardation syndrome 2017-09-08 criteria provided, single submitter clinical testing
Invitae RCV000578291 SCV000825226 likely pathogenic Epilepsy, hearing loss, and mental retardation syndrome 2018-06-28 criteria provided, single submitter clinical testing This variant, c.989_991delCAA, results in the deletion of 1 amino acid of the SPATA5 protein (p.Thr330del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs748291365, ExAC 0.02%), including one homozygous individual. This variant has been reported in individuals and families affected with microcephaly, intellectual disability, seizures, and hearing loss (PMID: 26299366, 27246907, 27683084, 28293831). ClinVar contains an entry for this variant (Variation ID: 207828). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Undiagnosed Diseases Network,NIH RCV000578291 SCV000837695 likely pathogenic Epilepsy, hearing loss, and mental retardation syndrome 2018-04-18 criteria provided, single submitter clinical testing

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