Submissions for variant NM_152594.3(SPRED1):c.1044T>C (p.Val348=)

gnomAD frequency: 0.81965  dbSNP: rs3751526

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000041236	SCV000058318	benign	not specified	2015-12-30	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041236	SCV000064927	benign	not specified	2012-03-14	criteria provided, single submitter	clinical testing	Val348Val in exon 7 of SPRED1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and it has been identified in 90% (6302/7020) of European American chromosomes and 69% (2574/3738) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS/; dbSNP rs3751526).
PreventionGenetics, part of Exact Sciences	RCV000041236	SCV000316207	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000034272	SCV000390797	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	RCV000041236	SCV000514743	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	RCV000034272	SCV000605258	benign	Legius syndrome	2024-11-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589810	SCV000699956	benign	not provided	2017-04-18	criteria provided, single submitter	clinical testing	Variant summary: The SPRED1 c.1044T>C (p.Val348Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. However, no published functional studies are available to confirm these predictions. This variant was found in 104813/121358 control chromosomes (45668 homozygotes) from ExAC at a frequency of 0.8636678; therefore it is a very common polymorphism and allele C is the major allele at this cDNA position. Several clinical diagnostic laboratories/reputable databases have classified this variant as benign. Taken together, this variant is classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000034272	SCV001000162	benign	Legius syndrome	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000034272	SCV002057653	benign	Legius syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002399365	SCV002704880	benign	Cardiovascular phenotype	2016-04-04	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	RCV000034272	SCV004015550	benign	Legius syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589810	SCV005296184	benign	not provided		criteria provided, single submitter	not provided
GeneReviews	RCV000034272	SCV000058212	not provided	Legius syndrome		no assertion provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000034272	SCV000733439	benign	Legius syndrome		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041236	SCV001920872	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000041236	SCV001931574	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000041236	SCV001957051	benign	not specified		no assertion criteria provided	clinical testing