Submissions for variant NM_000321.3(RB1):c.2566G>A (p.Asp856Asn)

gnomAD frequency: 0.00075  dbSNP: rs149359120

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000467622	SCV000562085	benign	Retinoblastoma	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492588	SCV000580829	likely benign	Hereditary cancer-predisposing syndrome	2018-12-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Mendelics	RCV000467622	SCV000838929	benign	Retinoblastoma	2023-08-22	criteria provided, single submitter	clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000761059	SCV000890974	uncertain significance	B Lymphoblastic Leukemia/Lymphoma, Not Otherwise Specified	2016-04-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000467622	SCV001267268	benign	Retinoblastoma	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	RCV001555707	SCV001777164	likely benign	not provided	2019-08-22	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23532519, 22180099)
Genetic Services Laboratory, University of Chicago	RCV001821379	SCV002070324	likely benign	not specified	2021-06-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000492588	SCV002530837	likely benign	Hereditary cancer-predisposing syndrome	2021-08-04	criteria provided, single submitter	curation
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001555707	SCV004562060	likely benign	not provided	2023-05-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925378	SCV004745638	likely benign	RB1-related condition	2022-08-26	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).