Variant: NM_177438.3(DICER1):c.4449G>A (p.Met1483Ile)

CA390868420

577152 (ClinVar)

Gene: DICER1

Condition: DICER1-related tumor predisposition

Inheritance Mode: Autosomal dominant inheritance

UUID: 7c2d7e8f-25f6-4005-b0cc-81f6f123334b

Approved on: 2024-01-09

Published on: 2024-01-17

HGVS expressions

NM_177438.3:c.4449G>A
NM_177438.3(DICER1):c.4449G>A (p.Met1483Ile)
NC_000014.9:g.95096471C>T
CM000676.2:g.95096471C>T
NC_000014.8:g.95562808C>T
CM000676.1:g.95562808C>T
NC_000014.7:g.94632561C>T
NG_016311.1:g.65952G>A
ENST00000343455.8:c.4449G>A
ENST00000393063.6:c.4449G>A
ENST00000526495.6:c.4449G>A
ENST00000532939.3:c.4449G>A
ENST00000556045.6:c.4449G>A
ENST00000675540.1:c.2194G>A
ENST00000675995.1:c.*2765G>A
ENST00000343455.7:c.4449G>A
ENST00000393063.5:c.4449G>A
ENST00000526495.5:c.4449G>A
ENST00000527414.5:c.4449G>A
ENST00000532939.2:c.484G>A
ENST00000541352.5:c.4449G>A
ENST00000556045.5:c.1143G>A
NM_001195573.1:c.4449G>A
NM_001271282.2:c.4449G>A
NM_001291628.1:c.4449G>A
NM_030621.4:c.4449G>A
NM_177438.2:c.4449G>A
NM_001271282.3:c.4449G>A
NM_001291628.2:c.4449G>A
NM_001395677.1:c.4449G>A
NM_001395678.1:c.4449G>A
NM_001395679.1:c.4449G>A
NM_001395680.1:c.4449G>A
NM_001395682.1:c.4449G>A
NM_001395683.1:c.4449G>A
NM_001395684.1:c.4449G>A
NM_001395685.1:c.4449G>A
NM_001395686.1:c.4167G>A
NM_001395687.1:c.4044G>A
NM_001395688.1:c.4044G>A
NM_001395689.1:c.4044G>A
NM_001395690.1:c.4044G>A
NM_001395691.1:c.3882G>A
NM_001395692.1:c.4449G>A
NM_001395693.1:c.4449G>A
NM_001395694.1:c.4449G>A
NM_001395695.1:c.4449G>A
NM_001395696.1:c.4044G>A
NM_001395697.1:c.2766G>A
NR_172715.1:n.4867G>A
NR_172716.1:n.5051G>A
NR_172717.1:n.4961G>A
NR_172718.1:n.4884G>A
NR_172719.1:n.4717G>A
NR_172720.1:n.4794G>A

Uncertain Significance

• Met criteria codes: BP4

• Not Met criteria codes: BA1 BS4 BS3 BS1 BS2 BP2 PS4 PS2 PS1 PS3 PP4 PP1 PP3 PM5 PM1 PM6 PM2

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 1.2.0

Evidence submitted by expert panel

DICER1 and miRNA-Processing Gene VCEP

The NM_177438.2:c.4449G>A variant in DICER1 is a missense variant predicted to cause substitution of methionine by isoleucine at amino acid 1483 (p.Met1483Ile). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00005782 (2/34590 alleles) in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.039; MaxEntScan and SpliceAI: no effect on splicing) (BP4). 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: BP4. (Bayesian Points: -1; VCEP specifications version 1.2.0; 01/09/2024).

Met criteria codes

• BP4: In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.039; MaxEntScan and SpliceAI: no effect on splicing) (BP4).

Not Met criteria codes

• BA1: 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
• BS2: 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
• PS4: 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
• PS1: 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
• 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
• 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
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: The highest population minor allele frequency in gnomAD v2.1.1 is 0.00005782 (2/34590 alleles) in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met).