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.1802T>C (p.Ile601Thr)

CA7331394

543609 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 90671796-2c83-4347-834c-9404ea96ad25
Approved on: 2025-01-07
Published on: 2025-01-27

HGVS expressions

NM_177438.3:c.1802T>C
NM_177438.3(DICER1):c.1802T>C (p.Ile601Thr)
NC_000014.9:g.95115772A>G
CM000676.2:g.95115772A>G
NC_000014.8:g.95582109A>G
CM000676.1:g.95582109A>G
NC_000014.7:g.94651862A>G
NG_016311.1:g.46651T>C
ENST00000529720.2:c.1802T>C
ENST00000531162.7:c.1802T>C
ENST00000674628.2:c.1802T>C
ENST00000675540.2:c.1802T>C
ENST00000696733.1:c.1802T>C
ENST00000696734.1:c.1802T>C
ENST00000696736.1:c.1802T>C
ENST00000696737.1:c.1802T>C
ENST00000696920.1:n.2065T>C
ENST00000696921.1:n.2908T>C
ENST00000696922.1:n.2211T>C
ENST00000696923.1:c.1802T>C
ENST00000696924.1:c.1802T>C
ENST00000696925.1:n.2211T>C
ENST00000696927.1:n.1397T>C
ENST00000696928.1:n.1999T>C
ENST00000343455.8:c.1802T>C
ENST00000393063.6:c.1802T>C
ENST00000526495.6:c.1802T>C
ENST00000532939.3:c.1802T>C
ENST00000556045.6:c.1802T>C
ENST00000675995.1:c.*118T>C
ENST00000343455.7:c.1802T>C
ENST00000393063.5:c.1802T>C
ENST00000526495.5:c.1802T>C
ENST00000527414.5:c.1802T>C
ENST00000532458.1:n.391T>C
ENST00000541352.5:c.1802T>C
NM_001195573.1:c.1802T>C
NM_001271282.2:c.1802T>C
NM_001291628.1:c.1802T>C
NM_030621.4:c.1802T>C
NM_177438.2:c.1802T>C
NM_001271282.3:c.1802T>C
NM_001291628.2:c.1802T>C
NM_001395677.1:c.1802T>C
NM_001395678.1:c.1802T>C
NM_001395679.1:c.1802T>C
NM_001395680.1:c.1802T>C
NM_001395682.1:c.1802T>C
NM_001395683.1:c.1802T>C
NM_001395684.1:c.1802T>C
NM_001395685.1:c.1802T>C
NM_001395686.1:c.1520T>C
NM_001395687.1:c.1397T>C
NM_001395688.1:c.1397T>C
NM_001395689.1:c.1397T>C
NM_001395690.1:c.1397T>C
NM_001395691.1:c.1235T>C
NM_001395692.1:c.1802T>C
NM_001395693.1:c.1802T>C
NM_001395694.1:c.1802T>C
NM_001395695.1:c.1802T>C
NM_001395696.1:c.1397T>C
NM_001395697.1:c.119T>C
NM_001395698.1:c.1397T>C
NR_172715.1:n.2220T>C
NR_172716.1:n.2147T>C
NR_172717.1:n.2314T>C
NR_172718.1:n.2314T>C
NR_172719.1:n.2147T>C
NR_172720.1:n.2147T>C
More

Likely Benign

Met criteria codes 2
BS2_Supporting BP4
Not Met criteria codes 22
PS2 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM4 PM3 PM5 PM6 PM2 PVS1 BS4 BS3 BS1 BP3 BP2 BP1 BP7 BP5

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.1802T>C variant in DICER1 is a missense variant predicted to cause substitution of isoleucine by threonine at amino acid 601 (p.Ile601Thr). 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 0.000007434 (12/1,614,166 alleles) with a highest population minor allele frequency of 0.00001017 (12/1,179,996 alleles) in 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: 0.033; 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_Supporting, BP4. (Bayesian Points: -2; 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).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.033; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
Not Met criteria codes
PS2
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
BA1
The total allele frequency in gnomAD v4.1.0 is 0.000007434 (12/1,614,166 alleles) with a highest population minor allele frequency of 0.00001017 (12/1,179,996 alleles) in European (Non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
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
PP2
This evidence code is not currently applicable for DICER1 VCEP curations.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
This evidence code is not currently applicable for DICER1 VCEP curations.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
This evidence code is not currently applicable for DICER1 VCEP curations.
PM2
The total allele frequency in gnomAD v4.1.0 is 0.000007434 (12/1,614,166 alleles) with a highest population minor allele frequency of 0.00001017 (12/1,179,996 alleles) in European (Non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PVS1
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
The total allele frequency in gnomAD v4.1.0 is 0.000007434 (12/1,614,166 alleles) with a highest population minor allele frequency of 0.00001017 (12/1,179,996 alleles) in European (Non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BP3
This evidence code is not currently applicable for DICER1 VCEP curations.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
This evidence code is not currently applicable for DICER1 VCEP curations.
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
This evidence code is not currently applicable for DICER1 VCEP curations.
Curation History
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