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

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

Met criteria codes 2
PM4_Supporting BS2
Not Met criteria codes 16
PP3 PP4 PM5 PM1 PM2 PS1 PS4 PS3 BA1 PVS1 BP7 BP5 BP4 BP2 BS3 BS1

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.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)
Met criteria codes
PM4_Supporting
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 (PM4_Supporting).
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.
Not Met criteria codes
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
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).
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).
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
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).
PVS1
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.
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
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).
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