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]
Link to SEPIO compliant JSON-LD document
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_177438.3(DICER1):c.128C>T (p.Thr43Met)

CA7331742

412157 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 6423dd38-27ed-45af-a327-2c64f2cada7d
Approved on: 2024-06-25
Published on: 2024-07-30

HGVS expressions

NM_177438.3:c.128C>T
NM_177438.3(DICER1):c.128C>T (p.Thr43Met)
NC_000014.9:g.95133331G>A
CM000676.2:g.95133331G>A
NC_000014.8:g.95599668G>A
CM000676.1:g.95599668G>A
NC_000014.7:g.94669421G>A
NG_016311.1:g.29092C>T
ENST00000529720.2:c.128C>T
ENST00000531162.7:c.128C>T
ENST00000674628.2:c.128C>T
ENST00000675540.2:c.128C>T
ENST00000696733.1:c.128C>T
ENST00000696734.1:c.128C>T
ENST00000696736.1:c.128C>T
ENST00000696737.1:c.128C>T
ENST00000696739.1:n.576C>T
ENST00000696740.1:c.128C>T
ENST00000696921.1:n.359C>T
ENST00000696922.1:n.537C>T
ENST00000696923.1:c.128C>T
ENST00000696924.1:c.128C>T
ENST00000696925.1:n.537C>T
ENST00000696928.1:n.325C>T
ENST00000343455.8:c.128C>T
ENST00000393063.6:c.128C>T
ENST00000526495.6:c.128C>T
ENST00000531162.6:c.128C>T
ENST00000532939.3:c.128C>T
ENST00000556045.6:c.128C>T
ENST00000674628.1:c.128C>T
ENST00000675995.1:c.128C>T
ENST00000343455.7:c.128C>T
ENST00000393063.5:c.128C>T
ENST00000526495.5:c.128C>T
ENST00000527414.5:c.128C>T
ENST00000529206.1:n.269C>T
ENST00000529720.1:c.128C>T
ENST00000531162.5:c.128C>T
ENST00000541352.5:c.128C>T
NM_001195573.1:c.128C>T
NM_001271282.2:c.128C>T
NM_001291628.1:c.128C>T
NM_030621.4:c.128C>T
NM_177438.2:c.128C>T
NM_001271282.3:c.128C>T
NM_001291628.2:c.128C>T
NM_001395677.1:c.128C>T
NM_001395678.1:c.128C>T
NM_001395679.1:c.128C>T
NM_001395680.1:c.128C>T
NM_001395682.1:c.128C>T
NM_001395683.1:c.128C>T
NM_001395684.1:c.128C>T
NM_001395685.1:c.128C>T
NM_001395686.1:c.-147C>T
NM_001395687.1:c.-130-654C>T
NM_001395688.1:c.-147C>T
NM_001395689.1:c.-147C>T
NM_001395690.1:c.-147C>T
NM_001395691.1:c.-331C>T
NM_001395692.1:c.128C>T
NM_001395693.1:c.128C>T
NM_001395694.1:c.128C>T
NM_001395695.1:c.128C>T
NM_001395696.1:c.-147C>T
NM_001395697.1:c.-1441C>T
NM_001395698.1:c.-147C>T
NM_001395699.1:c.128C>T
NM_001395700.1:c.128C>T
NR_172715.1:n.473C>T
NR_172716.1:n.473C>T
NR_172717.1:n.640C>T
NR_172718.1:n.640C>T
NR_172719.1:n.473C>T
NR_172720.1:n.473C>T

Likely Benign

Met criteria codes 2
BS2_Supporting BP4
Not Met criteria codes 19
PS2 PS4 PS3 PS1 PP1 PP3 PM1 PM4 PM5 PM6 PM2 PVS1 BA1 BS4 BS3 BS1 BP7 BP2 BP3

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_177438.2:c.128C>T variant in DICER1 is a missense variant predicted to cause substitution of threonine by methionine at amino acid 43 (p.Thr43Met). 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). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.429; MaxEntScan and SpliceAI: no effect on splicing) (BP4). The highest population minor allele frequency in gnomAD v4.1.0 is 0.0002667 (16/59982 alleles) in Admixed American population (PM2_Supporting, BS1, and BA1 are not met). 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_Supporting, BP4. (Bayesian Points: -2; VCEP specifications version 1.3.0; 06/25/2024)
Met criteria codes
BS2_Supporting
2 labs met BS2_supporting (tumor-free through 50) criteria.
BP4
REVEL = 0.429 (<50) and no splicing impact is predicted.
Not Met criteria codes
PS2
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
PS3
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
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
PM1
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
PM5
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
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
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
0.0002667 (16/59982) in Admix American and 0.00004392 (4/91074) in South American. gnomAD v.4.1.0.
BP7
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
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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