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_177438.2(DICER1):c.2650+1G>T

CA10586440

254310 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d11eed01-6066-4ff2-8cb6-624cd9cf9ceb
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.2650+1G>T
NM_177438.2(DICER1):c.2650+1G>T
NC_000014.9:g.95107879C>A
CM000676.2:g.95107879C>A
NC_000014.8:g.95574216C>A
CM000676.1:g.95574216C>A
NC_000014.7:g.94643969C>A
NG_016311.1:g.54544G>T
ENST00000343455.8:c.2650+1G>T
ENST00000393063.6:c.2650+1G>T
ENST00000526495.6:c.2650+1G>T
ENST00000532939.3:c.2650+1G>T
ENST00000556045.6:c.2650+1G>T
ENST00000675540.1:n.472+1G>T
ENST00000675995.1:c.*966+1G>T
ENST00000343455.7:c.2650+1G>T
ENST00000393063.5:c.2650+1G>T
ENST00000526495.5:c.2650+1G>T
ENST00000527414.5:c.2650+1G>T
ENST00000541352.5:c.2650+1G>T
NM_001195573.1:c.2650+1G>T
NM_001271282.2:c.2650+1G>T
NM_001291628.1:c.2650+1G>T
NM_030621.4:c.2650+1G>T
NM_001271282.3:c.2650+1G>T
NM_001291628.2:c.2650+1G>T
NM_177438.3:c.2650+1G>T
NM_001395677.1:c.2650+1G>T
NM_001395678.1:c.2650+1G>T
NM_001395679.1:c.2650+1G>T
NM_001395680.1:c.2650+1G>T
NM_001395682.1:c.2650+1G>T
NM_001395683.1:c.2650+1G>T
NM_001395684.1:c.2650+1G>T
NM_001395685.1:c.2650+1G>T
NM_001395686.1:c.2368+1G>T
NM_001395687.1:c.2245+1G>T
NM_001395688.1:c.2245+1G>T
NM_001395689.1:c.2245+1G>T
NM_001395690.1:c.2245+1G>T
NM_001395691.1:c.2083+1G>T
NM_001395692.1:c.2650+1G>T
NM_001395693.1:c.2650+1G>T
NM_001395694.1:c.2650+1G>T
NM_001395695.1:c.2650+1G>T
NM_001395696.1:c.2245+1G>T
NM_001395697.1:c.967+1G>T
NR_172715.1:n.3068+1G>T
NR_172716.1:n.2995+1G>T
NR_172717.1:n.3162+1G>T
NR_172718.1:n.3162+1G>T
NR_172719.1:n.2995+1G>T
NR_172720.1:n.2995+1G>T
NM_177438.3(DICER1):c.2650+1G>T
More

Pathogenic

Met criteria codes 3
PVS1 PM2_Supporting PS4_Moderate
Not Met criteria codes 4
BA1 BS3 BS1 PS3

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
The NM_177438.2:c.2650+1G>T variant in DICER1 occurs within the canonical splice donor (+/- 1) of intron 16 (PVS1). This variant received a total of 2 phenotype points across 2 unrelated probands meeting DICER1 VCEP phenotype specificity scoring criteria of 2-3.5 points (PMIDs: 26925222, 26925222, Internal lab contributors) (PS4_Moderate). This variant is absent from gnomAD v2.1.1 and v.3.1.1 (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_Moderate, PM2_Supporting. (Bayesian Points: 11; VCEP specifications version 1; 02/11/2022)
Met criteria codes
PVS1
Canonical GT donor splice variant in intron 16. Occurs before p.Pro1850. Exon is present in NM_177438.2.
PM2_Supporting
Absent in gnomAD. Coverage is >20X.
PS4_Moderate
2 Points; Reported in an individual with PPB type 1 (Brenneman et al. 2015. PMID: 26925222; 1 point); Detected in an Individual with Sertoli-Leydig tumor at <18 years, thyroid nodules at <18 years, renal cyst at <18 years by PreventionGenetics (1 point); Detected in an individual with PPB type 1 at <1 year (Likely same individual from PMID 26925222; 0 points); Detected in an unaffected individual with a positive family history by GeneDx (Not counted; 0 points).
Not Met criteria codes
BA1
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
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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