Submissions for variant NM_152594.3(SPRED1):c.424-8C>A

gnomAD frequency: 0.82015  dbSNP: rs7180446

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000041243	SCV000058322	benign	not specified	2015-09-10	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041243	SCV000064934	benign	not specified	2012-03-14	criteria provided, single submitter	clinical testing	424-8C>A in intron 4 of SPRED1: This variant is not expected to have clinical si gnificance because it has been identified in 90% (6302/7020) of European America n chromosomes and 69% (2574/3738) of African American chromosomes from a broad p opulation by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EV S/; dbSNP rs7180446).
PreventionGenetics, part of Exact Sciences	RCV000041243	SCV000316211	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000288944	SCV000390788	benign	Legius syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000041243	SCV000514742	benign	not specified	2015-07-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000288944	SCV000605257	benign	Legius syndrome	2023-11-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586606	SCV000699960	benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing	Variant summary: The SPRED1 c.424-8C>A variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 104727/121254 control chromosomes (45629 homozygotes) from ExAC at a frequency of 0.8636993 at a frequency of 0.8636993, which is approximately 345479 times the estimated maximal expected allele frequency of a pathogenic SPRED1 variant (0.0000025), therefore this variant is a benign common polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Invitae	RCV000288944	SCV001000161	benign	Legius syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000288944	SCV002057650	benign	Legius syndrome	2021-07-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000288944	SCV004015549	benign	Legius syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000288944	SCV000733438	benign	Legius syndrome		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041243	SCV001921080	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000041243	SCV001958094	benign	not specified		no assertion criteria provided	clinical testing