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]
Link to SEPIO compliant JSON-LD document

Variant: NM_177438.2(DICER1):c.5521C>T (p.Leu1841=)

CA487843671

477262 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: fb6feb96-61c7-4b2b-92c3-e9bb04a80283
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.5521C>T
NM_177438.2(DICER1):c.5521C>T (p.Leu1841=)
NC_000014.9:g.95091209G>A
CM000676.2:g.95091209G>A
NC_000014.8:g.95557546G>A
CM000676.1:g.95557546G>A
NC_000014.7:g.94627299G>A
NG_016311.1:g.71214C>T
ENST00000343455.8:c.5521C>T
ENST00000393063.6:c.5521C>T
ENST00000526495.6:c.5521C>T
ENST00000556045.6:c.*238C>T
ENST00000675540.1:n.3266C>T
ENST00000675995.1:c.*3837C>T
ENST00000343455.7:c.5521C>T
ENST00000393063.5:c.5521C>T
ENST00000526495.5:c.5521C>T
ENST00000527414.5:c.5521C>T
ENST00000527416.2:n.114C>T
ENST00000527554.2:n.214C>T
ENST00000541352.5:c.5365-100C>T
ENST00000556045.5:c.2215C>T
NM_001195573.1:c.5365-100C>T
NM_001271282.2:c.5521C>T
NM_001291628.1:c.5521C>T
NM_030621.4:c.5521C>T
NM_001271282.3:c.5521C>T
NM_001291628.2:c.5521C>T
NM_177438.3:c.5521C>T
NM_001395677.1:c.5521C>T
NM_001395678.1:c.5521C>T
NM_001395679.1:c.5521C>T
NM_001395680.1:c.5521C>T
NM_001395682.1:c.5521C>T
NM_001395683.1:c.5521C>T
NM_001395684.1:c.5521C>T
NM_001395685.1:c.5521C>T
NM_001395686.1:c.5239C>T
NM_001395687.1:c.5116C>T
NM_001395688.1:c.5116C>T
NM_001395689.1:c.5116C>T
NM_001395690.1:c.5116C>T
NM_001395691.1:c.4954C>T
NM_001395697.1:c.3838C>T
NR_172715.1:n.5939C>T
NR_172716.1:n.6123C>T
NR_172717.1:n.6033C>T
NR_172718.1:n.5956C>T
NR_172719.1:n.5789C>T
NR_172720.1:n.5992C>T
NM_177438.3(DICER1):c.5521C>T (p.Leu1841=)

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 3
BP7 BP4 PM2_Supporting
Not Met criteria codes 5
BS3 BS1 PS3 PP3 BA1

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

PDF
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.5521C>T (p.Leu1841=) variant is a synonymous (silent) variant that is not predicted by MaxEntScan or SpliceAI to impact splicing (BP4, BP7). This variant is absent from gnomAD v2.1.1 and v.3.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely benign for DICER1 syndrome. Although there are both pathogenic and benign types of evidence for this variant, the pathogenic evidence is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4, BP7, PM2_Supporting. (Bayesian Points: -1; VCEP specifications version 1; 02/11/22)
Met criteria codes
BP7
Variant is the reference nucleotide in 4 mammalian species. Concordance of SpliceAI and MES of no splicing effect.
BP4
Concordance of SpliceAI and MES of no splicing effect.
PM2_Supporting
Absent in gnomAD. Coverage is >20X.
Not Met criteria codes
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
PP3
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
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