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.2417C>T (p.Thr806Met)

CA7331249

412136 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: fb8a62ed-51c2-49c9-bd5b-26de274ad839
Approved on: 2025-01-07
Published on: 2025-01-27

HGVS expressions

NM_177438.3:c.2417C>T
NM_177438.3(DICER1):c.2417C>T (p.Thr806Met)
NC_000014.9:g.95108343G>A
CM000676.2:g.95108343G>A
NC_000014.8:g.95574680G>A
CM000676.1:g.95574680G>A
NC_000014.7:g.94644433G>A
NG_016311.1:g.54080C>T
ENST00000529720.2:c.2417C>T
ENST00000531162.7:c.2417C>T
ENST00000674628.2:c.2417C>T
ENST00000675540.2:c.2417C>T
ENST00000696733.1:c.2417C>T
ENST00000696734.1:c.2417C>T
ENST00000696736.1:c.2417C>T
ENST00000696737.1:c.2417C>T
ENST00000696738.1:n.305C>T
ENST00000696920.1:n.2680C>T
ENST00000696921.1:n.3523C>T
ENST00000696922.1:n.2826C>T
ENST00000696923.1:c.2417C>T
ENST00000696924.1:c.2417C>T
ENST00000696925.1:n.2826C>T
ENST00000696927.1:n.2012C>T
ENST00000343455.8:c.2417C>T
ENST00000393063.6:c.2417C>T
ENST00000526495.6:c.2417C>T
ENST00000532939.3:c.2417C>T
ENST00000556045.6:c.2417C>T
ENST00000675540.1:c.239C>T
ENST00000675995.1:c.*733C>T
ENST00000343455.7:c.2417C>T
ENST00000393063.5:c.2417C>T
ENST00000526495.5:c.2417C>T
ENST00000527414.5:c.2417C>T
ENST00000541352.5:c.2417C>T
NM_001195573.1:c.2417C>T
NM_001271282.2:c.2417C>T
NM_001291628.1:c.2417C>T
NM_030621.4:c.2417C>T
NM_177438.2:c.2417C>T
NM_001271282.3:c.2417C>T
NM_001291628.2:c.2417C>T
NM_001395677.1:c.2417C>T
NM_001395678.1:c.2417C>T
NM_001395679.1:c.2417C>T
NM_001395680.1:c.2417C>T
NM_001395682.1:c.2417C>T
NM_001395683.1:c.2417C>T
NM_001395684.1:c.2417C>T
NM_001395685.1:c.2417C>T
NM_001395686.1:c.2135C>T
NM_001395687.1:c.2012C>T
NM_001395688.1:c.2012C>T
NM_001395689.1:c.2012C>T
NM_001395690.1:c.2012C>T
NM_001395691.1:c.1850C>T
NM_001395692.1:c.2417C>T
NM_001395693.1:c.2417C>T
NM_001395694.1:c.2417C>T
NM_001395695.1:c.2417C>T
NM_001395696.1:c.2012C>T
NM_001395697.1:c.734C>T
NR_172715.1:n.2835C>T
NR_172716.1:n.2762C>T
NR_172717.1:n.2929C>T
NR_172718.1:n.2929C>T
NR_172719.1:n.2762C>T
NR_172720.1:n.2762C>T
More

Uncertain Significance

Met criteria codes 1
BS2_Supporting
Not Met criteria codes 8
PM2 PM1 PM5 BA1 BS1 BP4 PS4 PP3

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.2417C>T variant in DICER1 is a missense variant predicted to cause substitution of threonine by methionine at amino acid 806 (p.Thr806Met). Although this variant has been observed in germline cases, to our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition (PS4 not met; PMID: 33630087; Internal lab contributors). This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors). The total allele frequency in gnomAD v4.1.0 is 0.00001116(18/1613564 alleles) with a highest population minor allele frequency of 0.00003294 (3/91066 alleles) in the South Asian population (PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.746, which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function (PP3 and BP4 not met). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2_Supporting. (Bayesian Points: -1; VCEP specifications version 1.3.0; 01/07/2025)
Met criteria codes
BS2_Supporting
This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors).
Not Met criteria codes
PM2
The total allele frequency in gnomAD v4.1.0 is 0.00001116(18/1613564 alleles) with a highest population minor allele frequency of 0.00003294 (3/91066 alleles) in the South Asian population (PM2_Supporting, BS1, and BA1 are not met).
PM1
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).
PM5
No other missense variants at this codon have been reported in ClinVar at this time.
BA1
The total allele frequency in gnomAD v4.1.0 is 0.00001116(18/1613564 alleles) with a highest population minor allele frequency of 0.00003294 (3/91066 alleles) in the South Asian population (PM2_Supporting, BS1, and BA1 are not met).
BS1
The total allele frequency in gnomAD v4.1.0 is 0.00001116(18/1613564 alleles) with a highest population minor allele frequency of 0.00003294 (3/91066 alleles) in the South Asian population (PM2_Supporting, BS1, and BA1 are not met).
BP4
The computational predictor REVEL gives a score of 0.746, which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function (PP3 and BP4 not met).
PS4
Although this variant has been observed in germline cases, to our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition (PS4 not met; PMID: 33630087; Internal lab contributors). Seen in 4 individuals without specific features for DICER1-related disease (PMID: 33630087): Case 1: 60sy Male with “History of thyroid cancer” by ICD9 code; Case 2: 60sy Male with Sigmoid colon, Adenocarcinoma; Case 3: 60sy Female with Breast, infiltrating duct carcinoma; Case 4: 50sy Male with Intrahepatic bile duct, adenocarcinoma
PP3
The computational predictor REVEL gives a score of 0.746, which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function (PP3 and BP4 not met).
Curation History
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