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.5516G>A (p.Arg1839Gln)

CA158288

133976 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c2244761-5cda-4ad6-97d6-89d93ef19819
Approved on: 2025-06-24
Published on: 2025-07-08

HGVS expressions

NM_177438.3:c.5516G>A
NM_177438.3(DICER1):c.5516G>A (p.Arg1839Gln)
NC_000014.9:g.95091214C>T
CM000676.2:g.95091214C>T
NC_000014.8:g.95557551C>T
CM000676.1:g.95557551C>T
NC_000014.7:g.94627304C>T
NG_016311.1:g.71209G>A
ENST00000529720.2:c.5516G>A
ENST00000531162.7:c.5516G>A
ENST00000674628.2:c.5516G>A
ENST00000675540.2:c.*2166G>A
ENST00000696733.1:c.*138G>A
ENST00000696734.1:c.*171G>A
ENST00000696735.1:n.2503G>A
ENST00000696736.1:c.5516G>A
ENST00000696920.1:n.5779G>A
ENST00000696921.1:n.6622G>A
ENST00000696922.1:n.8447G>A
ENST00000696923.1:c.*171G>A
ENST00000696924.1:c.*138G>A
ENST00000696925.1:n.8447G>A
ENST00000343455.8:c.5516G>A
ENST00000393063.6:c.5516G>A
ENST00000526495.6:c.5516G>A
ENST00000556045.6:c.*233G>A
ENST00000675540.1:c.3261G>A
ENST00000675995.1:c.*3832G>A
ENST00000343455.7:c.5516G>A
ENST00000393063.5:c.5516G>A
ENST00000526495.5:c.5516G>A
ENST00000527414.5:c.5516G>A
ENST00000527416.2:n.109G>A
ENST00000527554.2:n.209G>A
ENST00000541352.5:c.5365-105G>A
ENST00000556045.5:c.2210G>A
NM_001195573.1:c.5365-105G>A
NM_001271282.2:c.5516G>A
NM_001291628.1:c.5516G>A
NM_030621.4:c.5516G>A
NM_177438.2:c.5516G>A
NM_001271282.3:c.5516G>A
NM_001291628.2:c.5516G>A
NM_001395677.1:c.5516G>A
NM_001395678.1:c.5516G>A
NM_001395679.1:c.5516G>A
NM_001395680.1:c.5516G>A
NM_001395682.1:c.5516G>A
NM_001395683.1:c.5516G>A
NM_001395684.1:c.5516G>A
NM_001395685.1:c.5516G>A
NM_001395686.1:c.5234G>A
NM_001395687.1:c.5111G>A
NM_001395688.1:c.5111G>A
NM_001395689.1:c.5111G>A
NM_001395690.1:c.5111G>A
NM_001395691.1:c.4949G>A
NM_001395697.1:c.3833G>A
NR_172715.1:n.5934G>A
NR_172716.1:n.6118G>A
NR_172717.1:n.6028G>A
NR_172718.1:n.5951G>A
NR_172719.1:n.5784G>A
NR_172720.1:n.5987G>A
More

Likely Benign

Met criteria codes 3
BP4 PM1_Supporting BS2
Not Met criteria codes 17
BP2 BP7 PS4 PS2 PS1 PS3 PP1 PP4 PP3 PVS1 PM5 PM4 PM2 BA1 BS4 BS3 BS1

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_177438.2:c.5516G>A variant in DICER1 is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 1839 (p.Arg1839Gln). This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2; Internal lab contributors). The total allele frequency in gnomAD v4.1.0 is 0.0001060 (171/1613922 alleles) with a highest population minor allele frequency of 0.0001415 (167/1180020 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). This variant resides within the RNase IIIb domain (PM1_Supporting; PMID: 31342592). The computational predictor REVEL gives a score of 0.234, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate 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 Likely Benign for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2, PM1_Supporting, BP4. (Bayesian Points: -4; VCEP specifications version 1.3.0; 06/24/2025)
Met criteria codes
BP4
The computational predictor REVEL gives a score of 0.234, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4).
PM1_Supporting
This variant resides within the RNase IIIb domain (PM1_Supporting; PMID: 31342592).
BS2
This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2; Internal lab contributors).
Not Met criteria codes
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
PS4
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
PS1
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
PP1
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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
2 different missense variants, c.5515C>G, p.Arg1839Gly and c.5515C>T, p.Arg1839Trp), in the same codon have been reported (ClinVar Variation ID: 1497494, 479634). However, these variants have not yet met the criteria to be classified as pathogenic by the ClinGen DICER VCEP (PM5 not met).
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The total allele frequency in gnomAD v4.1.0 is 0.0001060 (171/1613922 alleles) with a highest population minor allele frequency of 0.0001415 (167/1180020 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BA1
The total allele frequency in gnomAD v4.1.0 is 0.0001060 (171/1613922 alleles) with a highest population minor allele frequency of 0.0001415 (167/1180020 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BS4
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
The total allele frequency in gnomAD v4.1.0 is 0.0001060 (171/1613922 alleles) with a highest population minor allele frequency of 0.0001415 (167/1180020 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
Curation History
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