Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_177438.3(DICER1):c.2236A>G (p.Arg746Gly)

CA10586443

254305 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 8f6db0d5-993c-4af2-82c9-1793f0986d75
Approved on: 2025-10-28
Published on: 2025-11-13

HGVS expressions

NM_177438.3:c.2236A>G
NM_177438.3(DICER1):c.2236A>G (p.Arg746Gly)
NC_000014.9:g.95111337T>C
CM000676.2:g.95111337T>C
NC_000014.8:g.95577674T>C
CM000676.1:g.95577674T>C
NC_000014.7:g.94647427T>C
NG_016311.1:g.51086A>G
ENST00000529720.2:c.2236A>G
ENST00000531162.7:c.2236A>G
ENST00000674628.2:c.2236A>G
ENST00000675540.2:c.2236A>G
ENST00000696733.1:c.2236A>G
ENST00000696734.1:c.2236A>G
ENST00000696736.1:c.2236A>G
ENST00000696737.1:c.2236A>G
ENST00000696738.1:n.114A>G
ENST00000696920.1:n.2499A>G
ENST00000696921.1:n.3342A>G
ENST00000696922.1:n.2645A>G
ENST00000696923.1:c.2236A>G
ENST00000696924.1:c.2236A>G
ENST00000696925.1:n.2645A>G
ENST00000696927.1:n.1831A>G
ENST00000696928.1:n.2433A>G
ENST00000343455.8:c.2236A>G
ENST00000393063.6:c.2236A>G
ENST00000526495.6:c.2236A>G
ENST00000532939.3:c.2236A>G
ENST00000556045.6:c.2236A>G
ENST00000675540.1:c.58A>G
ENST00000675995.1:c.*552A>G
ENST00000343455.7:c.2236A>G
ENST00000393063.5:c.2236A>G
ENST00000526495.5:c.2236A>G
ENST00000527414.5:c.2236A>G
ENST00000541352.5:c.2236A>G
NM_001195573.1:c.2236A>G
NM_001271282.2:c.2236A>G
NM_001291628.1:c.2236A>G
NM_030621.4:c.2236A>G
NM_177438.2:c.2236A>G
NM_001271282.3:c.2236A>G
NM_001291628.2:c.2236A>G
NM_001395677.1:c.2236A>G
NM_001395678.1:c.2236A>G
NM_001395679.1:c.2236A>G
NM_001395680.1:c.2236A>G
NM_001395682.1:c.2236A>G
NM_001395683.1:c.2236A>G
NM_001395684.1:c.2236A>G
NM_001395685.1:c.2236A>G
NM_001395686.1:c.1954A>G
NM_001395687.1:c.1831A>G
NM_001395688.1:c.1831A>G
NM_001395689.1:c.1831A>G
NM_001395690.1:c.1831A>G
NM_001395691.1:c.1669A>G
NM_001395692.1:c.2236A>G
NM_001395693.1:c.2236A>G
NM_001395694.1:c.2236A>G
NM_001395695.1:c.2236A>G
NM_001395696.1:c.1831A>G
NM_001395697.1:c.553A>G
NM_001395698.1:c.1831A>G
NR_172715.1:n.2654A>G
NR_172716.1:n.2581A>G
NR_172717.1:n.2748A>G
NR_172718.1:n.2748A>G
NR_172719.1:n.2581A>G
NR_172720.1:n.2581A>G
More

Uncertain Significance

Met criteria codes 4
PM2_Supporting PS4_Supporting BP4 PS2
Not Met criteria codes 9
PM1 PM5 BA1 BS3 BS1 PS3 PS1 PP4 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen DICER1 and miRNA-Processing Gene Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DICER1 Version 1.4.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
DICER1 and miRNA-Processing Gene VCEP
The NM_177438.3:c.2236A>G variant in DICER1 is a missense variant predicted to cause substitution of arginine by glycine at amino acid 746 (p.Arg746Gly). This variant received a total of 1 phenotype point across 1 proband with pleuropulmonary blastoma, meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; PMID: 26925222). This observation was observed as a de novo occurrence with constitutional mosaicism (PS2; PMIDs:26925222). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational predictor REVEL gives a score of 0.409, which is below the threshold of 0.5, and the splice site predictor SpliceAI indicates that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as Uncertain Significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PS4_Supporting, PS2, PM2_Supporting, BP4. (Bayesian Points: 5; VCEP specifications version 1.4.0; 10/28/2025)
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PS4_Supporting
This variant received a total of 1 phenotype point across 1 proband meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; PMID: 26925222).
BP4
The computational predictor REVEL gives a score of 0.409, which is below the threshold of 0.5, and the splice site predictor SpliceAI indicates that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4).
PS2
This variant has been identified as a de novo occurrence with constitutional mosaicism in 1 individual with pleuropulmonary blastoma (PS2; PMIDs:26925222).
Not Met criteria codes
PM1
Not in any of the designated PM1 domains as per VCEP specs
PM5
c.2237G>T (p.Arg746Met) (ClinVar ID: 664439) is a VUS in ClinVar
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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