Submissions for variant NM_177438.3(DICER1):c.2997T>G (p.Leu999=)

gnomAD frequency: 0.01764  dbSNP: rs12018992

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000250840	SCV000314669	benign	not specified	2017-08-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000459105	SCV000389754	benign	DICER1-related tumor predisposition	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000459105	SCV000563395	benign	DICER1-related tumor predisposition	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000494220	SCV000581537	benign	Hereditary cancer-predisposing syndrome	2016-09-09	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.
GeneDx	RCV000250840	SCV000730731	benign	not specified	2017-02-04	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.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000250840	SCV001372155	likely benign	not specified	2019-07-01	criteria provided, single submitter	curation	ACMG criteria met: BS1, BP1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001800633	SCV001472890	benign	not provided	2023-11-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000250840	SCV002046813	benign	not specified	2021-04-02	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000250840	SCV002551534	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316446	SCV004017400	benign	Pleuropulmonary blastoma	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001800633	SCV005210860	likely benign	not provided		criteria provided, single submitter	not provided