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.2988-1G>T

CA390878663

429116 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c0e0986d-b551-4b3a-85fd-418e2f10cd19
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.2988-1G>T
NM_177438.2(DICER1):c.2988-1G>T
NC_000014.9:g.95105784C>A
CM000676.2:g.95105784C>A
NC_000014.8:g.95572121C>A
CM000676.1:g.95572121C>A
NC_000014.7:g.94641874C>A
NG_016311.1:g.56639G>T
ENST00000343455.8:c.2988-1G>T
ENST00000393063.6:c.2988-1G>T
ENST00000526495.6:c.2988-1G>T
ENST00000532939.3:c.2988-1G>T
ENST00000556045.6:c.2988-1G>T
ENST00000675540.1:n.810-1G>T
ENST00000675995.1:c.*1304-1G>T
ENST00000343455.7:c.2988-1G>T
ENST00000393063.5:c.2988-1G>T
ENST00000526495.5:c.2988-1G>T
ENST00000527414.5:c.2988-1G>T
ENST00000541352.5:c.2988-1G>T
ENST00000554367.1:n.197-1G>T
ENST00000556045.5:c.-242-1G>T
NM_001195573.1:c.2988-1G>T
NM_001271282.2:c.2988-1G>T
NM_001291628.1:c.2988-1G>T
NM_030621.4:c.2988-1G>T
NM_001271282.3:c.2988-1G>T
NM_001291628.2:c.2988-1G>T
NM_177438.3:c.2988-1G>T
NM_001395677.1:c.2988-1G>T
NM_001395678.1:c.2988-1G>T
NM_001395679.1:c.2988-1G>T
NM_001395680.1:c.2988-1G>T
NM_001395682.1:c.2988-1G>T
NM_001395683.1:c.2988-1G>T
NM_001395684.1:c.2988-1G>T
NM_001395685.1:c.2988-1G>T
NM_001395686.1:c.2706-1G>T
NM_001395687.1:c.2583-1G>T
NM_001395688.1:c.2583-1G>T
NM_001395689.1:c.2583-1G>T
NM_001395690.1:c.2583-1G>T
NM_001395691.1:c.2421-1G>T
NM_001395692.1:c.2988-1G>T
NM_001395693.1:c.2988-1G>T
NM_001395694.1:c.2988-1G>T
NM_001395695.1:c.2988-1G>T
NM_001395696.1:c.2583-1G>T
NM_001395697.1:c.1305-1G>T
NR_172715.1:n.3406-1G>T
NR_172716.1:n.3589G>T
NR_172717.1:n.3500-1G>T
NR_172718.1:n.3500-1G>T
NR_172719.1:n.3333-1G>T
NR_172720.1:n.3333-1G>T
NM_177438.3(DICER1):c.2988-1G>T
More

Pathogenic

Met criteria codes 4
PM2_Supporting PS2 PS4_Moderate PVS1
Not Met criteria codes 9
BS4 BS3 BS1 PS3 BA1 PP4 PP1 PM6 PM1

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.2988-1G>T variant in DICER1 occurs within the canonical splice acceptor site (- 1) of intron 18. It is predicted to cause skipping of biologically-relevant-exon 19/27, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been identified as a de novo occurrence with confirmed parental relationships in 1 individual(s) with DICER1-related phenotypes (PS2; SCV000824652.2). 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 (PS4_Moderate; SCV000824652.2, SCV000581526.3). 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, PS2, PS4_moderate, PM2_supporting. (Bayesian Points: 15; VCEP specifications version 1; 02/11/2022)
Met criteria codes
PM2_Supporting
Absent gnomAD v2.1.1 (non-cancer). Over 20x coverage in >90% individuals.
PS2
Seen in 1 individual with DICER1-related phenotypes (internal laboratory contributor)
PS4_Moderate
Seen in 2 individuals with DICER1-related phenotypes (internal laboratory contributors)
PVS1
Exon skipping or use of a cryptic splice site disrupts reading frame and is predicted to undergo NMD: Stop codon 5’ of p.Pro1850
Not Met criteria codes
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
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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