Submissions for variant NM_001079866.2(BCS1L):c.-49-539T>A

dbSNP: rs386833855

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000049824	SCV000800718	uncertain significance	GRACILE syndrome	2018-06-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003556129	SCV004293969	likely pathogenic	not provided	2023-06-18	criteria provided, single submitter	clinical testing	This variant is also known as c.-588T>A. This variant occurs in a non-coding region of the BCS1L gene. It does not change the encoded amino acid sequence of the BCS1L protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with GRACILE syndrome (PMID: 12215968, 22277166). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56411). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004700349	SCV005205528	uncertain significance	not specified	2024-06-24	criteria provided, single submitter	clinical testing	Variant summary: BCS1L c.-50+155T>A is located in the untranslated mRNA region upstream of the initiation codon. The frequency of this variant in the general population could not be determined as the technology used for large population databases (ExAC, gnomAD, ESP, 1000G) cannot detect variants of this type. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.-50+155T>A has been reported in the literature in hte compound heterozygous state in individuals affected with GRACILE Syndrome (e.g. Vispaa_2002, Lynn_2012). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. This variant is also known as c.-588T>A. The following publications have been ascertained in the context of this evaluation (PMID: 22277166, 12215968). ClinVar contains an entry for this variant (Variation ID: 56411). Based on the evidence outlined above, the variant was classified as uncertain significance.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049824	SCV000082233	probable-pathogenic	GRACILE syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.