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]

Variant: NM_030621.4(DICER1):c.1880_1883del (p.Ile627fs)

CA10586449

254298 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 5419647c-c9b7-4b0b-bc83-ace48c868142
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_030621.4:c.1880_1883del
NM_030621.4(DICER1):c.1880_1883del (p.Ile627fs)
NC_000014.9:g.95115694_95115697del
CM000676.2:g.95115694_95115697del
NC_000014.8:g.95582031_95582034del
CM000676.1:g.95582031_95582034del
NC_000014.7:g.94651784_94651787del
NG_016311.1:g.46729_46732del
ENST00000343455.8:c.1880_1883del
ENST00000393063.6:c.1880_1883del
ENST00000526495.6:c.1880_1883del
ENST00000532939.3:c.1880_1883del
ENST00000556045.6:c.1880_1883del
ENST00000675995.1:c.*196_*199del
ENST00000343455.7:c.1880_1883del
ENST00000393063.5:c.1880_1883del
ENST00000526495.5:c.1880_1883del
ENST00000527414.5:c.1880_1883del
ENST00000532458.1:n.469_472del
ENST00000541352.5:c.1880_1883del
NM_001195573.1:c.1880_1883del
NM_001271282.2:c.1880_1883del
NM_001291628.1:c.1880_1883del
NM_177438.2:c.1880_1883del
NM_001271282.3:c.1880_1883del
NM_001291628.2:c.1880_1883del
NM_177438.3:c.1880_1883del
NM_001395677.1:c.1880_1883del
NM_001395678.1:c.1880_1883del
NM_001395679.1:c.1880_1883del
NM_001395680.1:c.1880_1883del
NM_001395682.1:c.1880_1883del
NM_001395683.1:c.1880_1883del
NM_001395684.1:c.1880_1883del
NM_001395685.1:c.1880_1883del
NM_001395686.1:c.1598_1601del
NM_001395687.1:c.1475_1478del
NM_001395688.1:c.1475_1478del
NM_001395689.1:c.1475_1478del
NM_001395690.1:c.1475_1478del
NM_001395691.1:c.1313_1316del
NM_001395692.1:c.1880_1883del
NM_001395693.1:c.1880_1883del
NM_001395694.1:c.1880_1883del
NM_001395695.1:c.1880_1883del
NM_001395696.1:c.1475_1478del
NM_001395697.1:c.197_200del
NM_001395698.1:c.1475_1478del
NR_172715.1:n.2298_2301del
NR_172716.1:n.2225_2228del
NR_172717.1:n.2392_2395del
NR_172718.1:n.2392_2395del
NR_172719.1:n.2225_2228del
NR_172720.1:n.2225_2228del
NM_177438.3(DICER1):c.1880_1883del (p.Ile627fs)
More

Pathogenic

Met criteria codes 4
PS4_Supporting PP1 PVS1 PM2_Supporting
Not Met criteria codes 8
PS2 PS3 PP4 PM6 BA1 BS4 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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
DICER1 and miRNA-Processing Gene VCEP
NM_177438.2(DICER1):c.1880_1883del (p.Ile627fs) variant in DICER1 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 11/27 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant received a total of 1 phenotype point across 1 unrelated probands/families meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; PMIDs 26925222, ClinVar SCVs: SCV000581520.4, SCV000571419.5). The variant has been reported to segregate with disease in multiple affected family members, with 3 meioses from 1 family (PP1; ClinVar SCVs: SCV000581520.4). This variant is absent from gnomAD v2.1.1 and v3.1.1 (non-cancer)(PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PVS1, PS4_Supporting, PP1, PM2_Supporting (Bayesian Points: 11; VCEP specifications version 1; 02/11/2022).
Met criteria codes
PS4_Supporting
Total of 1 pt. Brenneman et al 2015/Ambry/GeneDx/NCI are all part of the same family.
PP1
3 meiosis
PVS1
Frameshift – 5’ of NMD cutoff (p.Pro1850)
PM2_Supporting
Absent in gnomAD with good coverage >90x
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
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
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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