Submissions for variant NM_003119.4(SPG7):c.1552+2dup

gnomAD frequency: 0.00001  dbSNP: rs1567928509

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Paris Brain Institute, Inserm - ICM	RCV001391523	SCV001451054	pathogenic	Hereditary spastic paraplegia 7		criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001664793	SCV001879861	uncertain significance	not provided	2020-10-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001664793	SCV002064532	likely pathogenic	not provided	2020-05-13	criteria provided, single submitter	clinical testing	DNA sequence analysis of the SPG7 gene demonstrated a sequence change near the canonical splice donor site of intron 11, c.1552+2dup. Based on in silico splice prediction programs, this sequence change likely affects normal splicing of the SPG7 gene, which would result in an abnormal protein (exon 11 skipping is possible). This particular sequence change has been described in the gnomAD database in one individual which corresponds to a population frequency of 0.00040%. This particular sequence change does not appear to have been described in the literature in other patients with SPG7 related disorders, however, a different splice site variant at the same position, c.1552+1G>T, has been described in the homozygous state in patient with spastic paraplegia. This change lead to an abnormally spliced mRNA lacking exon 11 (PMID: 20108356). These collective evidences indicate that this sequence change is likely pathogenic, however functional studies have not been performed to prove this conclusively.