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]
  • 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_177438.3(DICER1):c.2257-2A>G

CA390882450

1687238 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2fea624e-7809-49fa-8d98-b0bffb11baaf
Approved on: 2024-02-27
Published on: 2024-05-08

HGVS expressions

NM_177438.3:c.2257-2A>G
NM_177438.3(DICER1):c.2257-2A>G
NC_000014.9:g.95108505T>C
CM000676.2:g.95108505T>C
NC_000014.8:g.95574842T>C
CM000676.1:g.95574842T>C
NC_000014.7:g.94644595T>C
NG_016311.1:g.53918A>G
ENST00000529720.2:c.2257-2A>G
ENST00000531162.7:c.2257-2A>G
ENST00000674628.2:c.2257-2A>G
ENST00000675540.2:c.2257-2A>G
ENST00000696733.1:c.2257-2A>G
ENST00000696734.1:c.2257-2A>G
ENST00000696736.1:c.2257-2A>G
ENST00000696737.1:c.2257-2A>G
ENST00000696738.1:n.145-2A>G
ENST00000696920.1:n.2520-2A>G
ENST00000696921.1:n.3363-2A>G
ENST00000696922.1:n.2666-2A>G
ENST00000696923.1:c.2257-2A>G
ENST00000696924.1:c.2257-2A>G
ENST00000696925.1:n.2666-2A>G
ENST00000696927.1:n.1852-2A>G
ENST00000343455.8:c.2257-2A>G
ENST00000393063.6:c.2257-2A>G
ENST00000526495.6:c.2257-2A>G
ENST00000532939.3:c.2257-2A>G
ENST00000556045.6:c.2257-2A>G
ENST00000675540.1:c.79-2A>G
ENST00000675995.1:c.*573-2A>G
ENST00000343455.7:c.2257-2A>G
ENST00000393063.5:c.2257-2A>G
ENST00000526495.5:c.2257-2A>G
ENST00000527414.5:c.2257-2A>G
ENST00000541352.5:c.2257-2A>G
NM_001195573.1:c.2257-2A>G
NM_001271282.2:c.2257-2A>G
NM_001291628.1:c.2257-2A>G
NM_030621.4:c.2257-2A>G
NM_177438.2:c.2257-2A>G
NM_001271282.3:c.2257-2A>G
NM_001291628.2:c.2257-2A>G
NM_001395677.1:c.2257-2A>G
NM_001395678.1:c.2257-2A>G
NM_001395679.1:c.2257-2A>G
NM_001395680.1:c.2257-2A>G
NM_001395682.1:c.2257-2A>G
NM_001395683.1:c.2257-2A>G
NM_001395684.1:c.2257-2A>G
NM_001395685.1:c.2257-2A>G
NM_001395686.1:c.1975-2A>G
NM_001395687.1:c.1852-2A>G
NM_001395688.1:c.1852-2A>G
NM_001395689.1:c.1852-2A>G
NM_001395690.1:c.1852-2A>G
NM_001395691.1:c.1690-2A>G
NM_001395692.1:c.2257-2A>G
NM_001395693.1:c.2257-2A>G
NM_001395694.1:c.2257-2A>G
NM_001395695.1:c.2257-2A>G
NM_001395696.1:c.1852-2A>G
NM_001395697.1:c.574-2A>G
NR_172715.1:n.2675-2A>G
NR_172716.1:n.2602-2A>G
NR_172717.1:n.2769-2A>G
NR_172718.1:n.2769-2A>G
NR_172719.1:n.2602-2A>G
NR_172720.1:n.2602-2A>G
More

Uncertain Significance

Met criteria codes 3
PS4_Supporting PM2_Supporting PVS1_Moderate
Not Met criteria codes 12
PS2 PS3 BA1 PP4 PP1 PP3 PM6 BS4 BS3 BS1 BP2 BP4

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.2257-2A>G variant in DICER1 occurs within the canonical splice acceptor site of intron 14. It is predicted to cause skipping of biologically-relevant exon 15/27, resulting in an in-frame deletion, removing <10% of the protein (PVS1_Moderate). This variant received a total of 1 phenotype point across 2 unrelated probands meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; Internal lab contributors). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Uncertain Significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PS4_Supporting, PM2_Supporting, and PVS1_Moderate. (Bayesian Points: 4; VCEP specifications version 1.3.0; 02/27/2024)
Met criteria codes
PS4_Supporting
This variant received a total of 1 phenotype points across 2 unrelated probands meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; Internal lab contributors).
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PVS1_Moderate
The NM_177438.2:c.2257-2A>G variant in DICER1 occurs within the canonical splice acceptor site -2 of intron 14. It is predicted to cause skipping of biologically-relevant exon 15/27, resulting in an in-frame deletion, however, it is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate).
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
BA1
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
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Rule code cannot be used
PM6
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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