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_030621.4(DICER1):c.4178_4180dup (p.Asn1393dup)

Curation Version - 2.1
Curation History
JSON LD for Version 2.1

CA10583198

242100 (ClinVar)

Gene: DICER1

Condition: DICER1-related tumor predisposition

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ebc82eb3-d263-4c9b-88a4-5f3f2b7325cc

Approved on: 2024-08-27

Published on: 2024-09-16

HGVS expressions

NM_030621.4:c.4178_4180dup

NM_030621.4(DICER1):c.4178_4180dup (p.Asn1393dup)

NC_000014.9:g.95099808_95099810dup

CM000676.2:g.95099808_95099810dup

NC_000014.8:g.95566145_95566147dup

CM000676.1:g.95566145_95566147dup

NC_000014.7:g.94635898_94635900dup

NG_016311.1:g.62615_62617dup

ENST00000529720.2:c.4178_4180dup

ENST00000531162.7:c.4178_4180dup

ENST00000674628.2:c.4178_4180dup

ENST00000675540.2:c.*828_*830dup

ENST00000696733.1:c.4178_4180dup

ENST00000696734.1:c.4178_4180dup

ENST00000696735.1:n.1165_1167dup

ENST00000696736.1:c.4178_4180dup

ENST00000696737.1:c.4178_4180dup

ENST00000696920.1:n.4441_4443dup

ENST00000696921.1:n.5284_5286dup

ENST00000696922.1:n.4587_4589dup

ENST00000696923.1:c.4178_4180dup

ENST00000696924.1:c.4178_4180dup

ENST00000696925.1:n.4587_4589dup

ENST00000343455.8:c.4178_4180dup

ENST00000393063.6:c.4178_4180dup

ENST00000526495.6:c.4178_4180dup

ENST00000532939.3:c.4178_4180dup

ENST00000556045.6:c.4178_4180dup

ENST00000675540.1:c.1923_1925dup

ENST00000675995.1:c.*2494_*2496dup

ENST00000343455.7:c.4178_4180dup

ENST00000393063.5:c.4178_4180dup

ENST00000526495.5:c.4178_4180dup

ENST00000527414.5:c.4178_4180dup

ENST00000532939.2:c.213_215dup

ENST00000541352.5:c.4178_4180dup

ENST00000556045.5:c.872_874dup

NM_001195573.1:c.4178_4180dup

NM_001271282.2:c.4178_4180dup

NM_001291628.1:c.4178_4180dup

NM_177438.2:c.4178_4180dup

NM_001271282.3:c.4178_4180dup

NM_001291628.2:c.4178_4180dup

NM_177438.3:c.4178_4180dup

NM_001395677.1:c.4178_4180dup

NM_001395678.1:c.4178_4180dup

NM_001395679.1:c.4178_4180dup

NM_001395680.1:c.4178_4180dup

NM_001395682.1:c.4178_4180dup

NM_001395683.1:c.4178_4180dup

NM_001395684.1:c.4178_4180dup

NM_001395685.1:c.4178_4180dup

NM_001395686.1:c.3896_3898dup

NM_001395687.1:c.3773_3775dup

NM_001395688.1:c.3773_3775dup

NM_001395689.1:c.3773_3775dup

NM_001395690.1:c.3773_3775dup

NM_001395691.1:c.3611_3613dup

NM_001395692.1:c.4178_4180dup

NM_001395693.1:c.4178_4180dup

NM_001395694.1:c.4178_4180dup

NM_001395695.1:c.4178_4180dup

NM_001395696.1:c.3773_3775dup

NM_001395697.1:c.2495_2497dup

NR_172715.1:n.4596_4598dup

NR_172716.1:n.4780_4782dup

NR_172717.1:n.4690_4692dup

NR_172718.1:n.4613_4615dup

NR_172719.1:n.4446_4448dup

NR_172720.1:n.4523_4525dup

Likely Benign

BS2 PM4_Supporting

PVS1 PM2 PM5 PM1 BA1 BS3 BS1 BP4 BP2 BP7 BP5 PS1 PS4 PS3 PP3 PP4

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 1.3.0

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.4178_4180dup variant is predicted to cause a change in the length of the protein (p.Asn1393dup) due to an in-frame insertion of 1 amino acid in a non-repeat region outside of the RNase IIIb domain (p.D606-p.D609; p.E1418-p.E1420; p.E1422-p.E1425) (PM4_Supporting). 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 highest population minor allele frequency in gnomAD v4.1.0 is 0.00004417 (3/67924 alleles) in European (non-Finnish) 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: PM4_Supporting, BS2. (Bayesian Points: -3; VCEP specifications version 1.3.0; 08/27/2024)

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 GTRs: 500031, 61756). Invitae and Ambry internal data.

PM4_Supporting

PVS1

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 v4.1.0 is 0.00004417 (3/67924 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM1

This variant is not a missense variant and 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).

BA1

The highest population minor allele frequency in gnomAD v4.1.0 is 0.00004417 (3/67924 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).

BS3

None identified

BS1

The highest population minor allele frequency in gnomAD v4.1.0 is 0.00004417 (3/67924 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).

BP4

N/A - not a missense variant or a predicted splice variant. Splice predictors predict no impact.

BP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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.

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS4

Seen >150 times in internal lab data without DICER1 phenotypes.

PS3

None identified

PP3

N/A - not a missense variant or a predicted splice variant. Splice predictors predict no impact.

PP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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