ClinVar Miner

Submissions for variant NM_014844.5(TECPR2):c.2829del (p.Asn944fs)

dbSNP: rs1889895576
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001250127 SCV001335518 likely pathogenic Hereditary spastic paraplegia 49 2020-06-11 criteria provided, single submitter research This homozygous variant was identified by research trio-exome sequencing in a 5 year old boy with intellectual disability, epilepsy, sleep apnea and delayed myelination with white matter defects in cranial MRI. The parents were consanguineous (first-degree cousins). Both parents were heterozygous carriers for this variant. This frameshift variant c.2829del, p.(Asn944Thrfs*7) in exon 12/20 of TECPR2 has not been reported in the general population, in public mutation databases or in the literature. However, biallelic truncating or missense variants have been described to cause “Spastic paraplegia 49, autosomal recessive” (Oz-Levi et al. Am J Hum Genet. 2012, PMID: 23176824). The frameshifting variant c.2829del causes no mRNA decay as shown by RT-PCR and qPCR from PAXgene. Taken together, we classify this variant as likely pathogenic based on the ACMG recommendations (Richards et al., 2015, PMID 25741868; criteria: PVS1 PM2).
Labcorp Genetics (formerly Invitae), Labcorp RCV001250127 SCV003308007 pathogenic Hereditary spastic paraplegia 49 2022-02-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 973501). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 33847017). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn944Thrfs*7) in the TECPR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TECPR2 are known to be pathogenic (PMID: 23176824, 25590979).

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