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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_177438.3(DICER1):c.1745T>C (p.Ile582Thr)

CA7331435

254293 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a64b2236-86cb-4b45-840e-349d93b1faeb
Approved on: 2024-10-22
Published on: 2024-11-13

HGVS expressions

NM_177438.3:c.1745T>C
NM_177438.3(DICER1):c.1745T>C (p.Ile582Thr)
NC_000014.9:g.95116460A>G
CM000676.2:g.95116460A>G
NC_000014.8:g.95582797A>G
CM000676.1:g.95582797A>G
NC_000014.7:g.94652550A>G
NG_016311.1:g.45963T>C
ENST00000529720.2:c.1745T>C
ENST00000531162.7:c.1745T>C
ENST00000674628.2:c.1745T>C
ENST00000675540.2:c.1745T>C
ENST00000696733.1:c.1745T>C
ENST00000696734.1:c.1745T>C
ENST00000696736.1:c.1745T>C
ENST00000696737.1:c.1745T>C
ENST00000696920.1:n.2008T>C
ENST00000696921.1:n.2851T>C
ENST00000696922.1:n.2154T>C
ENST00000696923.1:c.1745T>C
ENST00000696924.1:c.1745T>C
ENST00000696925.1:n.2154T>C
ENST00000696927.1:n.1340T>C
ENST00000696928.1:n.1942T>C
ENST00000343455.8:c.1745T>C
ENST00000393063.6:c.1745T>C
ENST00000526495.6:c.1745T>C
ENST00000532939.3:c.1745T>C
ENST00000556045.6:c.1745T>C
ENST00000675995.1:c.*61T>C
ENST00000343455.7:c.1745T>C
ENST00000393063.5:c.1745T>C
ENST00000526495.5:c.1745T>C
ENST00000527414.5:c.1745T>C
ENST00000532458.1:n.334T>C
ENST00000541352.5:c.1745T>C
NM_001195573.1:c.1745T>C
NM_001271282.2:c.1745T>C
NM_001291628.1:c.1745T>C
NM_030621.4:c.1745T>C
NM_177438.2:c.1745T>C
NM_001271282.3:c.1745T>C
NM_001291628.2:c.1745T>C
NM_001395677.1:c.1745T>C
NM_001395678.1:c.1745T>C
NM_001395679.1:c.1745T>C
NM_001395680.1:c.1745T>C
NM_001395682.1:c.1745T>C
NM_001395683.1:c.1745T>C
NM_001395684.1:c.1745T>C
NM_001395685.1:c.1745T>C
NM_001395686.1:c.1463T>C
NM_001395687.1:c.1340T>C
NM_001395688.1:c.1340T>C
NM_001395689.1:c.1340T>C
NM_001395690.1:c.1340T>C
NM_001395691.1:c.1178T>C
NM_001395692.1:c.1745T>C
NM_001395693.1:c.1745T>C
NM_001395694.1:c.1745T>C
NM_001395695.1:c.1745T>C
NM_001395696.1:c.1340T>C
NM_001395697.1:c.62T>C
NM_001395698.1:c.1340T>C
NR_172715.1:n.2163T>C
NR_172716.1:n.2090T>C
NR_172717.1:n.2257T>C
NR_172718.1:n.2257T>C
NR_172719.1:n.2090T>C
NR_172720.1:n.2090T>C
More

Uncertain Significance

Met criteria codes 2
PS4_Supporting BP4
Not Met criteria codes 15
PS1 PS3 PS2 PP4 PP1 PP3 BA1 PM5 PM1 PM2 BS2 BS3 BS4 BS1 BP2

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 1.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
DICER1 and miRNA-Processing Gene VCEP
The NM_177438.3:c.1745T>C variant in DICER1 is a missense variant predicted to cause substitution of isoleucine by threonine at amino acid 582 (p.Ile582Thr). This variant received a total of 1 phenotype point(s) across 1 unrelated proband meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; PMID 26925222). The total allele frequency in gnomAD v4.1.0 is 0.000001861 (3/1611810 alleles) with a highest population minor allele frequency of 0.00003201 (2/62476 alleles) in a population of unknown ancestry (PM2_Supporting, BS1, and BA1 are not met). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.493; 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: PS4_Supporting, BP4. (Bayesian Points: 0; VCEP specifications version 1.3.0; 10/22/2024)
Met criteria codes
PS4_Supporting
This variant received a total of 1 phenotype point(s) across 1 unrelated proband meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; 26925222).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.493; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
Not Met criteria codes
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
PS2
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
Two different missense variants, c.1744A>T (p.Ile582Phe), and c.1744A>G (p.Ile582Val), in the same codon have been reported (ClinVar Variation ID: 2795248, ClinVar Variation ID: 1422894). However, these variants have not yet met the criteria to be classified as pathogenic by the ClinGen DICER1 VCEP (PM5 not met).
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The total allele frequency in gnomAD v4.1.0 is 0.000001861 (3/1611810 alleles) with a highest population minor allele frequency of 0.00003201 (2/62476 alleles) in "remaining" population (PM2_Supporting, BS1, and BA1 are not met).
BS2
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
BS4
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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