Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_177438.3(DICER1):c.4189T>C (p.Trp1397Arg)

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Curation History
JSON LD for Version 1.0

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

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

Likely Benign

BP4 BS2_Supporting

PM1 PM5 PM2 BA1 BS4 BS3 BS1 BP2 PS2 PS4 PS3 PS1 PP4 PP1 PP3

Evidence Links 0

Expert Panel

DICER1 and miRNA-Processing Gene VCEP

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)

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).

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).

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