Submissions for variant NM_014844.5(TECPR2):c.3275C>T (p.Ser1092Leu)

gnomAD frequency: 0.00388  dbSNP: rs72700618

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204784	SCV000262334	likely benign	Hereditary spastic paraplegia 49	2025-02-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001573949	SCV000730150	likely benign	not provided	2019-07-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001573949	SCV001961472	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	TECPR2: BS2
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847942	SCV002105941	likely benign	Hereditary spastic paraplegia	2020-07-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002517387	SCV003678576	likely benign	Inborn genetic diseases	2022-05-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689677	SCV005185330	likely benign	not specified	2024-05-08	criteria provided, single submitter	clinical testing	Variant summary: TECPR2 c.3275C>T (p.Ser1092Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.004 in 251446 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in TECPR2 causing Hereditary Spastic Paraplegia, Type 49 phenotype (0.0011), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3275C>T in individuals affected with Hereditary Spastic Paraplegia, Type 49 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 221132). Based on the evidence outlined above, the variant was classified as likely benign.
Breakthrough Genomics, Breakthrough Genomics	RCV001573949	SCV005211482	likely benign	not provided		criteria provided, single submitter	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573949	SCV001800556	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001573949	SCV001922110	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000204784	SCV002091144	benign	Hereditary spastic paraplegia 49	2019-12-10	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003967560	SCV004778756	likely benign	TECPR2-related disorder	2020-09-11	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).