Submissions for variant NM_145207.3(AFG2A):c.1073del (p.Gly357_Leu358insTer)

dbSNP: rs751291521

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413360	SCV000491701	likely pathogenic	not provided	2016-12-01	criteria provided, single submitter	clinical testing	The c.1073delT variant in the SPATA5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1073delT variant causes a frameshift, changing codon Leucine 358 to a premature Stop codon, denoted p.Leu358Ter. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1073delT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1073delT as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001238772	SCV001411601	pathogenic	Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	2022-09-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu358*) in the SPATA5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPATA5 are known to be pathogenic (PMID: 26299366). This variant is present in population databases (rs751291521, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SPATA5-related conditions. ClinVar contains an entry for this variant (Variation ID: 373135). For these reasons, this variant has been classified as Pathogenic.