Variant: NM_177438.3(DICER1):c.5382G>C (p.Glu1794Asp)

CA7330668

825692 (ClinVar)

Gene: DICER1

Condition: DICER1-related tumor predisposition

Inheritance Mode: Autosomal dominant inheritance

UUID: cbf08eec-ad66-4c79-bcc8-417313329560

Approved on: 2025-08-26

Published on: 2025-09-19

HGVS expressions

NM_177438.3:c.5382G>C
NM_177438.3(DICER1):c.5382G>C (p.Glu1794Asp)
NC_000014.9:g.95091348C>G
CM000676.2:g.95091348C>G
NC_000014.8:g.95557685C>G
CM000676.1:g.95557685C>G
NC_000014.7:g.94627438C>G
NG_016311.1:g.71075G>C
ENST00000529720.2:c.5382G>C
ENST00000531162.7:c.5382G>C
ENST00000674628.2:c.5382G>C
ENST00000675540.2:c.*2032G>C
ENST00000696733.1:c.*4G>C
ENST00000696734.1:c.*37G>C
ENST00000696735.1:n.2369G>C
ENST00000696736.1:c.5382G>C
ENST00000696920.1:n.5645G>C
ENST00000696921.1:n.6488G>C
ENST00000696922.1:n.8313G>C
ENST00000696923.1:c.*37G>C
ENST00000696924.1:c.*4G>C
ENST00000696925.1:n.8313G>C
ENST00000343455.8:c.5382G>C
ENST00000393063.6:c.5382G>C
ENST00000526495.6:c.5382G>C
ENST00000556045.6:c.*99G>C
ENST00000675540.1:c.3127G>C
ENST00000675995.1:c.*3698G>C
ENST00000343455.7:c.5382G>C
ENST00000393063.5:c.5382G>C
ENST00000526495.5:c.5382G>C
ENST00000527414.5:c.5382G>C
ENST00000527554.2:n.75G>C
ENST00000541352.5:c.5365-239G>C
ENST00000556045.5:c.2076G>C
NM_001195573.1:c.5365-239G>C
NM_001271282.2:c.5382G>C
NM_001291628.1:c.5382G>C
NM_030621.4:c.5382G>C
NM_177438.2:c.5382G>C
NM_001271282.3:c.5382G>C
NM_001291628.2:c.5382G>C
NM_001395677.1:c.5382G>C
NM_001395678.1:c.5382G>C
NM_001395679.1:c.5382G>C
NM_001395680.1:c.5382G>C
NM_001395682.1:c.5382G>C
NM_001395683.1:c.5382G>C
NM_001395684.1:c.5382G>C
NM_001395685.1:c.5382G>C
NM_001395686.1:c.5100G>C
NM_001395687.1:c.4977G>C
NM_001395688.1:c.4977G>C
NM_001395689.1:c.4977G>C
NM_001395690.1:c.4977G>C
NM_001395691.1:c.4815G>C
NM_001395697.1:c.3699G>C
NR_172715.1:n.5800G>C
NR_172716.1:n.5984G>C
NR_172717.1:n.5894G>C
NR_172718.1:n.5817G>C
NR_172719.1:n.5650G>C
NR_172720.1:n.5853G>C

Uncertain Significance

• Met criteria codes: PM2_Supporting PM1_Supporting BP4

• Not Met criteria codes: PP4 PP1 PP3 PM5 PM4 BS2 BS4 BS3 BS1 BP7 BP2 PVS1 PS4 PS2 PS3 PS1 BA1

Expert Panel

DICER1 and miRNA-Processing Gene VCEP

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

Evidence submitted by expert panel

DICER1 and miRNA-Processing Gene VCEP

The NM_177438.2:c.5382G>C variant in DICER1 is a missense variant predicted to cause substitution of Glutamic Acid by Aspartic Acid at amino acid 1794 (p.Glu1794Asp). Although this variant has been observed in individuals undergoing genetic sequencing, to our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition (PS4 not met; Internal lab contributors). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). This variant resides within the RNase IIIb domain of DICER1 (PM1_Supporting; PMID: 31342592). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.228: MaxEntScan and SpliceAI: no effect on splicing) (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: PM1_supporting, PM2_Supporting, BP4. (Bayesian Points: 1; VCEP specifications version 1.4.0, 08/26/2025).

Met criteria codes

• PM2_Supporting: This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
• PM1_Supporting: Residue in the RNase IIIb domain (p.Y1682 – p.S1846)
• BP4: REVEL score = 0.228. varSEAK Class 1 (No splicing effect). SpliceAI no change in Δ score (acceptor gain Δ score = 0.03; REF score = 0.51; ALT score = 0.53; pre-mRNA position = 12 bp).

Not Met criteria codes

• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: 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
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: Internal, unpublished functional data from assays not currently supported by ruleset. Evidence to be re-assessed when variant is reviewed for re-curation.
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: Although this variant has been observed in individuals undergoing genetic sequencing, to our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition (PS4 not met; Internal lab contributors).
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: Internal, unpublished functional data from assays not currently supported by ruleset. Evidence to be re-assessed when variant is reviewed for re-curation.
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline