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 computer assertion could be determined for this classification!

Variant: NM_177438.3(DICER1):c.5077C>A (p.His1693Asn)

CA390865930

479649 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 82d909cc-0578-43d5-b262-edaee45fea84
Approved on: 2024-02-27
Published on: 2024-05-08

HGVS expressions

NM_177438.3:c.5077C>A
NM_177438.3(DICER1):c.5077C>A (p.His1693Asn)
NC_000014.9:g.95095843G>T
CM000676.2:g.95095843G>T
NC_000014.8:g.95562180G>T
CM000676.1:g.95562180G>T
NC_000014.7:g.94631933G>T
NG_016311.1:g.66580C>A
ENST00000529720.2:c.5077C>A
ENST00000531162.7:c.5077C>A
ENST00000674628.2:c.5077C>A
ENST00000675540.2:c.*1727C>A
ENST00000696733.1:c.5077C>A
ENST00000696734.1:c.5077C>A
ENST00000696735.1:n.2064C>A
ENST00000696736.1:c.5077C>A
ENST00000696737.1:c.5077C>A
ENST00000696920.1:n.5340C>A
ENST00000696921.1:n.6183C>A
ENST00000696922.1:n.5486C>A
ENST00000696923.1:c.5077C>A
ENST00000696924.1:c.5077C>A
ENST00000696925.1:n.5486C>A
ENST00000343455.8:c.5077C>A
ENST00000393063.6:c.5077C>A
ENST00000526495.6:c.5077C>A
ENST00000532939.3:c.5077C>A
ENST00000556045.6:c.5077C>A
ENST00000675540.1:c.2822C>A
ENST00000675995.1:c.*3393C>A
ENST00000343455.7:c.5077C>A
ENST00000393063.5:c.5077C>A
ENST00000526495.5:c.5077C>A
ENST00000527414.5:c.5077C>A
ENST00000532939.2:c.1112C>A
ENST00000541352.5:c.5077C>A
ENST00000556045.5:c.1771C>A
NM_001195573.1:c.5077C>A
NM_001271282.2:c.5077C>A
NM_001291628.1:c.5077C>A
NM_030621.4:c.5077C>A
NM_177438.2:c.5077C>A
NM_001271282.3:c.5077C>A
NM_001291628.2:c.5077C>A
NM_001395677.1:c.5077C>A
NM_001395678.1:c.5077C>A
NM_001395679.1:c.5077C>A
NM_001395680.1:c.5077C>A
NM_001395682.1:c.5077C>A
NM_001395683.1:c.5077C>A
NM_001395684.1:c.5077C>A
NM_001395685.1:c.5077C>A
NM_001395686.1:c.4795C>A
NM_001395687.1:c.4672C>A
NM_001395688.1:c.4672C>A
NM_001395689.1:c.4672C>A
NM_001395690.1:c.4672C>A
NM_001395691.1:c.4510C>A
NM_001395692.1:c.5077C>A
NM_001395693.1:c.5077C>A
NM_001395694.1:c.5077C>A
NM_001395695.1:c.5077C>A
NM_001395696.1:c.4672C>A
NM_001395697.1:c.3394C>A
NR_172715.1:n.5495C>A
NR_172716.1:n.5679C>A
NR_172717.1:n.5589C>A
NR_172718.1:n.5512C>A
NR_172719.1:n.5345C>A
NR_172720.1:n.5422C>A
More

Uncertain Significance

Met criteria codes 3
PM2_Supporting PM1_Supporting BP4
Not Met criteria codes 14
PM5 BA1 BS2 BS4 BS3 BS1 BP2 PS2 PS3 PS4 PS1 PP4 PP1 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 1.3.0

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.5077C>A variant in DICER1 is a missense variant predicted to cause substitution of histidine by asparagine at amino acid 1693 (p.His1693Asn). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.476; MaxEntScan and SpliceAI: no effect on splicing) (BP4). This variant resides within the RNase IIIb mutational hotspot domain with critical functionality as defined by the ClinGen DICER1 VCEP (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: PM2_Supporting, BP4, PM1_Supporting. (Bayesian Points: 1; VCEP specifications version 1.3.0; 02/27/2024)
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PM1_Supporting
This variant resides within the RNase IIIb mutational hotspot domain with critical functionality as defined by the ClinGen DICER1 VCEP (PM1_Supporting; PMID: 31342592).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.476; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
Not Met criteria codes
PM5
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
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
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
PS2
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
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
Curation History
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