Variant: NM_177438.3(DICER1):c.238G>T (p.Glu80Ter)

Version: 2.0
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CA390889868

649946 (ClinVar)

Gene: DICER1 (HGNC:23405)

Condition: DICER1-related tumor predisposition

Inheritance Mode: Autosomal dominant inheritance

UUID: 23ee9f03-2243-4d18-b1eb-aec9c811e84f

Approved on: 2024-08-27

Published on: 2024-09-16

HGVS expressions

NM_177438.3:c.238G>T
NM_177438.3(DICER1):c.238G>T (p.Glu80Ter)
NC_000014.9:g.95132584C>A
CM000676.2:g.95132584C>A
NC_000014.8:g.95598921C>A
CM000676.1:g.95598921C>A
NC_000014.7:g.94668674C>A
NG_016311.1:g.29839G>T
ENST00000529720.2:c.238G>T
ENST00000531162.7:c.238G>T
ENST00000674628.2:c.238G>T
ENST00000675540.2:c.238G>T
ENST00000696733.1:c.238G>T
ENST00000696734.1:c.238G>T
ENST00000696736.1:c.238G>T
ENST00000696737.1:c.238G>T
ENST00000696739.1:n.686G>T
ENST00000696740.1:c.238G>T
ENST00000696921.1:n.469G>T
ENST00000696922.1:n.647G>T
ENST00000696923.1:c.238G>T
ENST00000696924.1:c.238G>T
ENST00000696925.1:n.647G>T
ENST00000696928.1:n.435G>T
ENST00000343455.8:c.238G>T
ENST00000393063.6:c.238G>T
ENST00000526495.6:c.238G>T
ENST00000531162.6:c.238G>T
ENST00000532939.3:c.238G>T
ENST00000556045.6:c.238G>T
ENST00000674628.1:c.238G>T
ENST00000675995.1:c.238G>T
ENST00000343455.7:c.238G>T
ENST00000393063.5:c.238G>T
ENST00000526495.5:c.238G>T
ENST00000527414.5:c.238G>T
ENST00000529206.1:n.379G>T
ENST00000541352.5:c.238G>T
NM_001195573.1:c.238G>T
NM_001271282.2:c.238G>T
NM_001291628.1:c.238G>T
NM_030621.4:c.238G>T
NM_177438.2:c.238G>T
NM_001271282.3:c.238G>T
NM_001291628.2:c.238G>T
NM_001395677.1:c.238G>T
NM_001395678.1:c.238G>T
NM_001395679.1:c.238G>T
NM_001395680.1:c.238G>T
NM_001395682.1:c.238G>T
NM_001395683.1:c.238G>T
NM_001395684.1:c.238G>T
NM_001395685.1:c.238G>T
NM_001395686.1:c.-37G>T
NM_001395687.1:c.-37G>T
NM_001395688.1:c.-37G>T
NM_001395689.1:c.-37G>T
NM_001395690.1:c.-37G>T
NM_001395691.1:c.-221G>T
NM_001395692.1:c.238G>T
NM_001395693.1:c.238G>T
NM_001395694.1:c.238G>T
NM_001395695.1:c.238G>T
NM_001395696.1:c.-37G>T
NM_001395697.1:c.-1331G>T
NM_001395698.1:c.-37G>T
NM_001395699.1:c.238G>T
NM_001395700.1:c.238G>T
NR_172715.1:n.583G>T
NR_172716.1:n.583G>T
NR_172717.1:n.750G>T
NR_172718.1:n.750G>T
NR_172719.1:n.583G>T
NR_172720.1:n.583G>T

Likely Pathogenic

• Met criteria codes: PVS1 PM2_Supporting

• Not Met criteria codes: PM6 PM1 PM3 PM5 PM4 BA1 BS2 BS1 BS4 BS3 BP5 BP7 BP4 BP3 BP1 BP2 PS1 PS2 PS3 PS4 PP1 PP2 PP3 PP4

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.238G>T (p.Glu80Ter) variant in DICER1 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant exon 3/27 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PVS1, PM2_supporting. (Bayesian Points: 9; VCEP specifications version 1.3.0; 08/27/2024)

Met criteria codes

• PVS1: Predicted to undergo NMD: Stop codon 5’ of p.Pro1850; UniProt: Helicase ATP-binding domain from p.51-227; This variant in exon 3. Start codon in exon 2. Second methionine is at p.11. The NM_177438.2:c.238G>T (p.Glu80Ter) variant in DICER1 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant exon 3/27 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
• PM2_Supporting: This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

Not Met criteria codes

• PM6: This evidence code is not currently applicable for DICER1 VCEP curations.
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: This evidence code is not currently applicable for DICER1 VCEP curations.
• PM5: 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
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS2: N/A
• BS1: 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
• BP5: This evidence code is not currently applicable for DICER1 VCEP curations.
• BP7: 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
• BP3: This evidence code is not currently applicable for DICER1 VCEP curations.
• BP1: This evidence code is not currently applicable for DICER1 VCEP curations.
• BP2: 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
• 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
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: This evidence code is not currently applicable for DICER1 VCEP curations.
• 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