Submissions for variant NM_152594.3(SPRED1):c.675C>T (p.Ser225=)

gnomAD frequency: 0.00092  dbSNP: rs144764225

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041245	SCV000064936	benign	not specified	2015-10-08	criteria provided, single submitter	clinical testing	p.Ser225Ser in exon 6 of SPRED1: This variant is not expected to have clinical s ignificance because it has been identified in 0.15% (23/15804) of South Asian ch romosomes and 0.13% (84/64292) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs144764225), does not alter an amino acid residue and is not located within the splice consensus seque nce.
Invitae	RCV001086681	SCV000260336	benign	Legius syndrome	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000586803	SCV000524538	benign	not provided	2016-11-23	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586803	SCV000699963	benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing	Variant summary: The SPRED1 c.675C>T (p.Ser225Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 124/117138 control chromosomes from ExAC at a frequency of 0.0010586, which is approximately 423 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 benign. Taken together, this variant is classified as Benign.
Illumina Laboratory Services, Illumina	RCV001086681	SCV001280218	likely benign	Legius syndrome	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813370	SCV002060699	benign	Noonan syndrome and Noonan-related syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002371855	SCV002667888	benign	Cardiovascular phenotype	2014-12-24	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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001086681	SCV004015551	benign	Legius syndrome	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586803	SCV004136300	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	SPRED1: BP4, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001086681	SCV004564789	benign	Legius syndrome	2023-08-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003974922	SCV004791833	likely benign	SPRED1-related disorder	2019-03-01	criteria provided, single submitter	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).
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000041245	SCV001799551	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041245	SCV001918803	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000586803	SCV001955685	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000586803	SCV001968928	likely benign	not provided		no assertion criteria provided	clinical testing