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

CA390864253

947388 (ClinVar)

Gene: DICER1

Condition: DICER1-related tumor predisposition

Inheritance Mode: Autosomal dominant inheritance

UUID: 69cd03ac-1108-485f-a535-21f331b4dd9f

Approved on: 2024-08-27

Published on: 2024-09-16

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
ENST00000529720.2:c.5563C>T
ENST00000531162.7:c.5563C>T
ENST00000674628.2:c.5563C>T
ENST00000675540.2:c.*2213C>T
ENST00000696733.1:c.*185C>T
ENST00000696734.1:c.*218C>T
ENST00000696735.1:n.2550C>T
ENST00000696736.1:c.5563C>T
ENST00000696920.1:n.5826C>T
ENST00000696921.1:n.6669C>T
ENST00000696922.1:n.8494C>T
ENST00000696923.1:c.*218C>T
ENST00000696924.1:c.*185C>T
ENST00000696925.1:n.8494C>T
ENST00000343455.8:c.5563C>T
ENST00000393063.6:c.5563C>T
ENST00000526495.6:c.5563C>T
ENST00000556045.6:c.*280C>T
ENST00000675540.1:c.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

Uncertain Significance

• Met criteria codes: PVS1_Moderate PM2_Supporting

• Not Met criteria codes: PP3 PP4 PP1 PS1 PS2 PS4 PS3 PM4 PM5 PM1 BA1 BP4 BP2 BP7 BS2 BS4 BS3 BS1

Expert Panel

DICER1 and miRNA-Processing Gene VCEP

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

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 has an allele frequency of 6.196e-7 (1/1613828 alleles) across gnomAD v4.1.0 with no more than one allele in any subpopulation, which is lower than the ClinGen DICER1 VCEP threshold (<0.000005) for PM2_Supporting, and therefore meets this criterion (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 variant meets the criteria to be classified as Uncertain Significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PVS1_Moderate, PM2_Supporting. (Bayesian Points: 3; VCEP specifications version 1.3.0; 08/27/2024)

Met criteria codes

• PVS1_Moderate: 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).
• PM2_Supporting: This variant has an allele frequency of 6.196e-7 (1/1613828 alleles) across gnomAD v4.1.0 with no more than one allele in any subpopulation, which is lower than the ClinGen DICER1 VCEP threshold (<0.000005) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).

Not Met criteria codes

• PP3: 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
• PS1: 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
• PS3: 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: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: 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
• BP4: 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
• 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