Submissions for variant NM_177438.3(DICER1):c.884C>G (p.Ser295Cys)

gnomAD frequency: 0.00001  dbSNP: rs548231008

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen	RCV000229795	SCV002540817	benign	DICER1-related tumor predisposition	2022-05-18	reviewed by expert panel	curation	The NM_177438.2:c.884C>G variant in DICER1 is a missense variant predicted to cause substitution of serine by cysteine at amino acid 295 (p.Ser295Cys). The highest population minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.0072 (219/30496 alleles; FAF=0.0064) in the South Asian population, which is higher than the ClinGen DICER1 VCEP threshold (>0.003) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as BENIGN for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BA1. (Bayesian Points: NA; VCEP specifications version 1; 02/11/2022)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000229795	SCV000291728	benign	DICER1-related tumor predisposition	2024-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000566029	SCV000661873	likely benign	Hereditary cancer-predisposing syndrome	2018-08-31	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Illumina Laboratory Services, Illumina	RCV000229795	SCV001276286	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.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000851486	SCV001371966	likely benign	not specified	2019-07-01	criteria provided, single submitter	curation	ACMG criteria met: PP5, BS1, BS2, BP1
Sema4, Sema4	RCV000566029	SCV002533087	benign	Hereditary cancer-predisposing syndrome	2020-10-12	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000851486	SCV002551566	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000851486	SCV002774323	benign	not specified	2021-07-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003891824	SCV000993774	benign	DICER1-related disorder	2022-07-22	no assertion criteria provided	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).