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.4189T>C (p.Trp1397Arg)

CA7330936

242101 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f575b0a3-4c52-42c6-8b73-5db64e531ea3
Approved on: 2024-01-09
Published on: 2024-01-17

HGVS expressions

NM_177438.3:c.4189T>C
NM_177438.3(DICER1):c.4189T>C (p.Trp1397Arg)
NC_000014.9:g.95099797A>G
CM000676.2:g.95099797A>G
NC_000014.8:g.95566134A>G
CM000676.1:g.95566134A>G
NC_000014.7:g.94635887A>G
NG_016311.1:g.62626T>C
ENST00000529720.2:c.4189T>C
ENST00000531162.7:c.4189T>C
ENST00000674628.2:c.4189T>C
ENST00000675540.2:c.*839T>C
ENST00000696733.1:c.4189T>C
ENST00000696734.1:c.4189T>C
ENST00000696735.1:n.1176T>C
ENST00000696736.1:c.4189T>C
ENST00000696737.1:c.4189T>C
ENST00000696920.1:n.4452T>C
ENST00000696921.1:n.5295T>C
ENST00000696922.1:n.4598T>C
ENST00000696923.1:c.4189T>C
ENST00000696924.1:c.4189T>C
ENST00000696925.1:n.4598T>C
ENST00000343455.8:c.4189T>C
ENST00000393063.6:c.4189T>C
ENST00000526495.6:c.4189T>C
ENST00000532939.3:c.4189T>C
ENST00000556045.6:c.4189T>C
ENST00000675540.1:c.1934T>C
ENST00000675995.1:c.*2505T>C
ENST00000343455.7:c.4189T>C
ENST00000393063.5:c.4189T>C
ENST00000526495.5:c.4189T>C
ENST00000527414.5:c.4189T>C
ENST00000532939.2:c.224T>C
ENST00000541352.5:c.4189T>C
ENST00000556045.5:c.883T>C
NM_001195573.1:c.4189T>C
NM_001271282.2:c.4189T>C
NM_001291628.1:c.4189T>C
NM_030621.4:c.4189T>C
NM_177438.2:c.4189T>C
NM_001271282.3:c.4189T>C
NM_001291628.2:c.4189T>C
NM_001395677.1:c.4189T>C
NM_001395678.1:c.4189T>C
NM_001395679.1:c.4189T>C
NM_001395680.1:c.4189T>C
NM_001395682.1:c.4189T>C
NM_001395683.1:c.4189T>C
NM_001395684.1:c.4189T>C
NM_001395685.1:c.4189T>C
NM_001395686.1:c.3907T>C
NM_001395687.1:c.3784T>C
NM_001395688.1:c.3784T>C
NM_001395689.1:c.3784T>C
NM_001395690.1:c.3784T>C
NM_001395691.1:c.3622T>C
NM_001395692.1:c.4189T>C
NM_001395693.1:c.4189T>C
NM_001395694.1:c.4189T>C
NM_001395695.1:c.4189T>C
NM_001395696.1:c.3784T>C
NM_001395697.1:c.2506T>C
NR_172715.1:n.4607T>C
NR_172716.1:n.4791T>C
NR_172717.1:n.4701T>C
NR_172718.1:n.4624T>C
NR_172719.1:n.4457T>C
NR_172720.1:n.4534T>C
More

Likely Benign

Met criteria codes 2
BS2_Supporting BP4
Not Met criteria codes 15
PS1 PS2 PS3 PS4 PP1 PP3 PP4 PM2 PM1 PM5 BA1 BS1 BS4 BS3 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 1.2.0

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.4189T>C variant in DICER1 is a missense variant predicted to cause substitution of tryptophan by arginine at amino acid 1397 (p.Trp1397Arg). The highest population minor allele frequency in gnomAD v3.1.2 is 0.00002462 (1/40622 alleles) in African/African American population (PM2_Supporting, BS1, and BA1 are not met). 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: 61756, 500031). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.207; 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 1.2.0; 01/09/2024)
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: 61756, 500031).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.207; 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
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
PS4
This variant received a total of 0.5 phenotype points in a single proband. (PS4 not met; Internal lab contributor: 500031).
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population minor allele frequency in gnomAD v3.1.2 is 0.00002462 (1/40622 alleles) in African/African American 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 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
BS1
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
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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