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.5515C>T (p.Arg1839Trp)

CA390864480

479634 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: b1bd01ae-8a55-4501-acbc-f73bb1c52494
Approved on: 2025-06-24
Published on: 2025-07-08

HGVS expressions

NM_177438.3:c.5515C>T
NM_177438.3(DICER1):c.5515C>T (p.Arg1839Trp)
NC_000014.9:g.95091215G>A
CM000676.2:g.95091215G>A
NC_000014.8:g.95557552G>A
CM000676.1:g.95557552G>A
NC_000014.7:g.94627305G>A
NG_016311.1:g.71208C>T
ENST00000529720.2:c.5515C>T
ENST00000531162.7:c.5515C>T
ENST00000674628.2:c.5515C>T
ENST00000675540.2:c.*2165C>T
ENST00000696733.1:c.*137C>T
ENST00000696734.1:c.*170C>T
ENST00000696735.1:n.2502C>T
ENST00000696736.1:c.5515C>T
ENST00000696920.1:n.5778C>T
ENST00000696921.1:n.6621C>T
ENST00000696922.1:n.8446C>T
ENST00000696923.1:c.*170C>T
ENST00000696924.1:c.*137C>T
ENST00000696925.1:n.8446C>T
ENST00000343455.8:c.5515C>T
ENST00000393063.6:c.5515C>T
ENST00000526495.6:c.5515C>T
ENST00000556045.6:c.*232C>T
ENST00000675540.1:c.3260C>T
ENST00000675995.1:c.*3831C>T
ENST00000343455.7:c.5515C>T
ENST00000393063.5:c.5515C>T
ENST00000526495.5:c.5515C>T
ENST00000527414.5:c.5515C>T
ENST00000527416.2:n.108C>T
ENST00000527554.2:n.208C>T
ENST00000541352.5:c.5365-106C>T
ENST00000556045.5:c.2209C>T
NM_001195573.1:c.5365-106C>T
NM_001271282.2:c.5515C>T
NM_001291628.1:c.5515C>T
NM_030621.4:c.5515C>T
NM_177438.2:c.5515C>T
NM_001271282.3:c.5515C>T
NM_001291628.2:c.5515C>T
NM_001395677.1:c.5515C>T
NM_001395678.1:c.5515C>T
NM_001395679.1:c.5515C>T
NM_001395680.1:c.5515C>T
NM_001395682.1:c.5515C>T
NM_001395683.1:c.5515C>T
NM_001395684.1:c.5515C>T
NM_001395685.1:c.5515C>T
NM_001395686.1:c.5233C>T
NM_001395687.1:c.5110C>T
NM_001395688.1:c.5110C>T
NM_001395689.1:c.5110C>T
NM_001395690.1:c.5110C>T
NM_001395691.1:c.4948C>T
NM_001395697.1:c.3832C>T
NR_172715.1:n.5933C>T
NR_172716.1:n.6117C>T
NR_172717.1:n.6027C>T
NR_172718.1:n.5950C>T
NR_172719.1:n.5783C>T
NR_172720.1:n.5986C>T
More

Uncertain Significance

Met criteria codes 3
BP4 BS2_Supporting PM1_Supporting
Not Met criteria codes 17
BA1 BS3 BS4 BS1 BP2 BP7 PS3 PS2 PS4 PS1 PP4 PP1 PP3 PM4 PM5 PM2 PVS1

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 1.3.0

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.5515C>T variant in DICER1 is a missense variant predicted to cause substitution of arginine by tryptophan at amino acid 1839 (p.Arg1839Trp). This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors). The total allele frequency in gnomAD v4.1.0 is 0.00001363 (22/1613858 alleles) with a highest population minor allele frequency of 0.00006402 (4/62482 alleles) in a population of unknown ancestry (PM2_Supporting, BS1, and BA1 are not met). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.398; MaxEntScan and SpliceAI: no effect on splicing) (BP4). This variant resides within the RNase IIIb domain (PM1_Supporting; PMID: 31342592). Due to conflicting evidence, this variant is classified as Uncertain Significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2_Supporting, BP4, PM1_Supporting. (Bayesian Points: -1; VCEP specifications version 1.3.0; 06/24/2025)
Met criteria codes
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.398; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
BS2_Supporting
This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors).
PM1_Supporting
This variant resides within the RNase IIIb domain (PM1_Supporting; PMID: 31342592).
Not Met criteria codes
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
BS4
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
BP2
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
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
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
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
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
2 different missense variants, c.5516G>A (p.Arg1839Gln) and c.5515C>G (p.Arg1839Gly), in the same codon have been reported (ClinVar Variation IDs: 133976, 1497494]. However, these variants have not yet met the criteria to be classified as pathogenic by the ClinGen DICER VCEP (PM5 not met).
PM2
The total allele frequency in gnomAD v4.1.0 is 0.00001363 (22/1613858 alleles) with a highest population minor allele frequency of 0.00006402 (4/62482 alleles) in a population of unknown ancestry (PM2_Supporting, BS1, and BA1 are not met).
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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