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.179C>T (p.Thr60Ile)

CA158267

133968 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2089884b-f9e8-4e9e-9b25-b13868f7a9ff
Approved on: 2025-01-07
Published on: 2025-01-27

HGVS expressions

NM_177438.3:c.179C>T
NM_177438.3(DICER1):c.179C>T (p.Thr60Ile)
NC_000014.9:g.95132643G>A
CM000676.2:g.95132643G>A
NC_000014.8:g.95598980G>A
CM000676.1:g.95598980G>A
NC_000014.7:g.94668733G>A
NG_016311.1:g.29780C>T
ENST00000529720.2:c.179C>T
ENST00000531162.7:c.179C>T
ENST00000674628.2:c.179C>T
ENST00000675540.2:c.179C>T
ENST00000696733.1:c.179C>T
ENST00000696734.1:c.179C>T
ENST00000696736.1:c.179C>T
ENST00000696737.1:c.179C>T
ENST00000696739.1:n.627C>T
ENST00000696740.1:c.179C>T
ENST00000696921.1:n.410C>T
ENST00000696922.1:n.588C>T
ENST00000696923.1:c.179C>T
ENST00000696924.1:c.179C>T
ENST00000696925.1:n.588C>T
ENST00000696928.1:n.376C>T
ENST00000343455.8:c.179C>T
ENST00000393063.6:c.179C>T
ENST00000526495.6:c.179C>T
ENST00000531162.6:c.179C>T
ENST00000532939.3:c.179C>T
ENST00000556045.6:c.179C>T
ENST00000674628.1:c.179C>T
ENST00000675995.1:c.179C>T
ENST00000343455.7:c.179C>T
ENST00000393063.5:c.179C>T
ENST00000526495.5:c.179C>T
ENST00000527414.5:c.179C>T
ENST00000529206.1:n.320C>T
ENST00000529720.1:c.179C>T
ENST00000531162.5:c.179C>T
ENST00000541352.5:c.179C>T
NM_001195573.1:c.179C>T
NM_001271282.2:c.179C>T
NM_001291628.1:c.179C>T
NM_030621.4:c.179C>T
NM_177438.2:c.179C>T
NM_001271282.3:c.179C>T
NM_001291628.2:c.179C>T
NM_001395677.1:c.179C>T
NM_001395678.1:c.179C>T
NM_001395679.1:c.179C>T
NM_001395680.1:c.179C>T
NM_001395682.1:c.179C>T
NM_001395683.1:c.179C>T
NM_001395684.1:c.179C>T
NM_001395685.1:c.179C>T
NM_001395686.1:c.-96C>T
NM_001395687.1:c.-96C>T
NM_001395688.1:c.-96C>T
NM_001395689.1:c.-96C>T
NM_001395690.1:c.-96C>T
NM_001395691.1:c.-280C>T
NM_001395692.1:c.179C>T
NM_001395693.1:c.179C>T
NM_001395694.1:c.179C>T
NM_001395695.1:c.179C>T
NM_001395696.1:c.-96C>T
NM_001395697.1:c.-1390C>T
NM_001395698.1:c.-96C>T
NM_001395699.1:c.179C>T
NM_001395700.1:c.179C>T
NR_172715.1:n.524C>T
NR_172716.1:n.524C>T
NR_172717.1:n.691C>T
NR_172718.1:n.691C>T
NR_172719.1:n.524C>T
NR_172720.1:n.524C>T
More

Likely Benign

Met criteria codes 2
BS2 BP4
Not Met criteria codes 10
PM2 PM1 BA1 BS4 BS1 BP2 PS2 PS4 PP4 PP1

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.179C>T variant in DICER1 is a missense variant predicted to cause substitution of threonine by isoleucine at amino acid 60 (p.Thr60Ile). 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; PMIDs: 29399970, 37019617, 24728327, Internal lab contributors). This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2; Internal lab contributors). The total allele frequency in gnomAD v4.1.0 is 0.0001599 (258/1613772 alleles) with a highest population minor allele frequency of 0.0002144 (253/1179916 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.32; MaxEntScan and SpliceAI: no effect on splicing) (BP4). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2, BP4. (Bayesian Points: -5; VCEP specifications version 1.3.0; 01/07/2025)
Met criteria codes
BS2
This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2; Internal lab contributors).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.32; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
Not Met criteria codes
PM2
The total allele frequency in gnomAD v4.1.0 is 0.0001599 (258/1613772 alleles) with a highest population minor allele frequency of 0.0002144 (253/1179916 alleles) in the European (non-Finnish) 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 critical functional domain by the ClinGen DICER1 VCEP (PM1 not met).
BA1
The total allele frequency in gnomAD v4.1.0 is 0.0001599 (258/1613772 alleles) with a highest population minor allele frequency of 0.0002144 (253/1179916 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
The total allele frequency in gnomAD v4.1.0 is 0.0001599 (258/1613772 alleles) with a highest population minor allele frequency of 0.0002144 (253/1179916 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BP2
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
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; PMIDs: 29399970, 37019617, 24728327, Internal lab contributors). This variant received 0 phenotype points across hundreds of internal and published observations (Internal lab contributors; PMIDs: 29399970, 37019617, 24728327)
PP4
This variant was observed in an individual with a thyroid nodule (30s) that harbored a somatic DICER1 hit p.E1813C. While p.E1813 is a recognized DICER1 hotspot codon, the specific variant p.E1813C has not been previously reported. (PP4 not met)
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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