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]

Variant: NM_177438.3(DICER1):c.5563C>T (p.Arg1855Ter)

CA390864253

947388 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 69cd03ac-1108-485f-a535-21f331b4dd9f
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.3:c.5563C>T
NM_177438.3(DICER1):c.5563C>T (p.Arg1855Ter)
NC_000014.9:g.95091074G>A
CM000676.2:g.95091074G>A
NC_000014.8:g.95557411G>A
CM000676.1:g.95557411G>A
NC_000014.7:g.94627164G>A
NG_016311.1:g.71349C>T
ENST00000343455.8:c.5563C>T
ENST00000393063.6:c.5563C>T
ENST00000526495.6:c.5563C>T
ENST00000556045.6:c.*280C>T
ENST00000675540.1:n.3308C>T
ENST00000675995.1:c.*3879C>T
ENST00000343455.7:c.5563C>T
ENST00000393063.5:c.5563C>T
ENST00000526495.5:c.5563C>T
ENST00000527414.5:c.5563C>T
ENST00000527416.2:n.156C>T
ENST00000527554.2:n.256C>T
ENST00000541352.5:c.5400C>T
ENST00000556045.5:c.2257C>T
NM_001195573.1:c.5400C>T
NM_001271282.2:c.5563C>T
NM_001291628.1:c.5563C>T
NM_030621.4:c.5563C>T
NM_177438.2:c.5563C>T
NM_001271282.3:c.5563C>T
NM_001291628.2:c.5563C>T
NM_001395677.1:c.5563C>T
NM_001395678.1:c.5563C>T
NM_001395679.1:c.5563C>T
NM_001395680.1:c.5563C>T
NM_001395682.1:c.5563C>T
NM_001395683.1:c.5563C>T
NM_001395684.1:c.5563C>T
NM_001395685.1:c.*109C>T
NM_001395686.1:c.5281C>T
NM_001395687.1:c.5158C>T
NM_001395688.1:c.5158C>T
NM_001395689.1:c.5158C>T
NM_001395690.1:c.5158C>T
NM_001395691.1:c.4996C>T
NM_001395697.1:c.3880C>T
NR_172715.1:n.5981C>T
NR_172716.1:n.6165C>T
NR_172717.1:n.6075C>T
NR_172718.1:n.5998C>T
NR_172719.1:n.5831C>T
NR_172720.1:n.6034C>T
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Uncertain Significance

Met criteria codes 2
PVS1_Moderate PM2_Supporting
Not Met criteria codes 11
PP1 PP4 BS1 BS4 BS3 BP2 PS2 PS3 PS4 PM6 PM1

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

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.5563C>T (p.Arg1855Ter) variant in DICER1 is a nonsense variant that may cause loss of function of the protein; however, it is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate). This variant is absent from gnomAD non-cancer datasets v2.1.1 and v3.1.1 (PM2_Supporting). This variant does not reside within a region of the RNAse IIIb domain that is defined as a mutational hotspot or critical functional domain by the ClinGen DICER1 VCEP (PM1 not met). In summary, this clinical significance is uncertain for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PVS1_moderate; PM2_supporting. (Bayesian Points: 3; VCEP specifications version 1; 02/11/2022)
Met criteria codes
PVS1_Moderate
Disrupts 68 of 1922 amino acids (<193 AAs)
PM2_Supporting
Absent from gnomAD
Not Met criteria codes
PP1
No reports found in the literature. All reported internal cases with no pertinent phenotype.
PP4
No tumor data found in literature of available in internal cases
BS1
Absent from gnomAD
BS4
No reports found in the literature. All reported internal cases with no pertinent phenotype.
BS3
No splicing impact on VarSeak/MES or SpliceAI.
BP2
No reports found in the literature. All reported internal cases with no pertinent phenotype.
PS2
No reports found in the literature. All reported internal cases with no pertinent phenotype.
PS3
No splicing impact on VarSeak/MES or SpliceAI.
PS4
No reports found in the literature. All reported internal cases with no pertinent phenotype.
PM6
No reports found in the literature. All reported internal cases with no pertinent phenotype.
PM1
Variant is not a missense and is not in hotspot
Curation History
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