Submissions for variant NM_152594.3(SPRED1):c.926T>C (p.Val309Ala)

gnomAD frequency: 0.00204  dbSNP: rs114636635

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154849	SCV000204531	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Val309Ala in Exon 07 of SPRED1: This variant is not expected to have clinical significance because it has been identified in 0.6% (21/3738) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs114636635).
Invitae	RCV000456632	SCV000560562	benign	Legius syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586323	SCV000699951	benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing	Variant summary: The SPRED1 c.926T>C (p.Val309Ala) variant involves the alteration of a conserved nucleotide and is predicted to be benign by 3/5 in silico tools. This variant was found in 81/121216 control chromosomes from ExAC at a frequency of 0.0006682, which is approximately 267 times the estimated maximal expected allele frequency of a pathogenic SPRED1 variant (0.0000025), therefore this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign and it is also classified as likely benign in a publication with an indication of benign functional outcome (Brems_2012). Taken together, this variant is classified as benign.
GeneDx	RCV000586323	SCV000730787	likely benign	not provided	2021-04-15	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21548021, 22753041)
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000456632	SCV000782327	uncertain significance	Legius syndrome	2016-11-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000456632	SCV001274827	benign	Legius syndrome	2017-10-15	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813401	SCV002060702	benign	Noonan syndrome and Noonan-related syndrome	2021-04-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004019853	SCV003650009	benign	Cardiovascular phenotype	2023-01-27	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000456632	SCV000692375	uncertain significance	Legius syndrome	2014-12-08	no assertion criteria provided	clinical testing