ClinVar Miner

Submissions for variant NM_014844.5(TECPR2):c.715G>A (p.Gly239Arg)

gnomAD frequency: 0.00004  dbSNP: rs750922939
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001070390 SCV001235617 uncertain significance Hereditary spastic paraplegia 49 2022-03-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 239 of the TECPR2 protein (p.Gly239Arg). This variant is present in population databases (rs750922939, gnomAD 0.07%). This missense change has been observed in individual(s) with clinical features of hereditary spastic paraplegia (PMID: 33847017). ClinVar contains an entry for this variant (Variation ID: 863424). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute of Human Genetics, University of Leipzig Medical Center RCV001070390 SCV001365388 uncertain significance Hereditary spastic paraplegia 49 2020-06-27 criteria provided, single submitter research This variant was identified compound heterozygous with the variant NM_014844.4:c.4033G>C, p.(Ala1345Pro) by research trio-exome sequencing in a 15 year old girl with intellectual disability, dystonic limb movements, spasticity, ataxia and abnormal gyration pattern in cranial MRI. The variant is paternally inherited. The family is from European descent. This missense variant c.715G>A, p.(Gly239Arg) in exon 6/20 of the TECPR2 has not been reported in public mutation databases or in the literature. In the general population the minor allele frequency is 0.00007424 (gnomAD). 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). Multiple in silico-tools predict this variant as damaging. Two splicing predicition tools indicate a possible new splice site (SpliceSiteFinder-like, MaxEntScan). Taken together, we classify this variant as of unknown significance based on the ACMG recommendations (Richards et al., 2015, PMID 25741868; criteria: PM2 PP3).
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV002291293 SCV002583687 uncertain significance not provided 2022-09-13 criteria provided, single submitter clinical testing PM2, PP3
Fulgent Genetics, Fulgent Genetics RCV001070390 SCV002776805 uncertain significance Hereditary spastic paraplegia 49 2021-07-22 criteria provided, single submitter clinical testing
Natera, Inc. RCV001070390 SCV001461364 uncertain significance Hereditary spastic paraplegia 49 2020-01-24 no assertion criteria provided clinical testing

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