Submissions for variant NM_002838.5(PTPRC):c.1568A>T (p.Glu523Val)

gnomAD frequency: 0.00241  dbSNP: rs116464756

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000757704	SCV000715340	likely benign	not provided	2018-08-31	criteria provided, single submitter	clinical testing
Invitae	RCV000640083	SCV000761671	likely benign	Immunodeficiency 104	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757704	SCV000886029	uncertain significance	not provided	2017-08-15	criteria provided, single submitter	clinical testing	The p.Glu523Val variant (rs116464756) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an African population frequency of 0.8 percent (identified on 193 out of 24,032 chromosomes).The glutamic acid at position 523 is weakly conserved (Alamut v.2.9.0) but computational analyses of the effects of the p.Glu523Val variant on protein structure and function provide conflicting results (SIFT: damaging, MutationTaster: polymorphism, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Glu523Val variant with certainty.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000640083	SCV000898919	uncertain significance	Immunodeficiency 104	2018-12-03	criteria provided, single submitter	clinical testing	PTPRC NM_002838.4 exon 14 p.Glu523Val (c.1568A>T): This variant has not been reported in the literature and is present in 0.8% (203/24962) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/1-198687340-A-T). This variant is present in ClinVar (Variation ID:506974). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224346	SCV003920366	uncertain significance	Immunodeficiency 105	2021-03-30	criteria provided, single submitter	clinical testing	PTPRC: NM_002838 exon 14 p.Glu523Val (c.1568A>T): This variant has not been reported in the literature but is present in 0.8% (193/24032) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs116464756). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
PreventionGenetics, part of Exact Sciences	RCV003915764	SCV004733254	benign	PTPRC-related condition	2019-07-31	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).