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.3019C>T (p.Gln1007Ter)

CA390878423

429113 (ClinVar)

Gene: DICER1 (HGNC:23405)
Condition: dicer1 syndrome (MONDO:0017288)
Inheritance Mode: Autosomal dominant inheritance
UUID: a06f071b-cc61-42ee-8dcd-c4aad03f7af7
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.3019C>T
NM_177438.2(DICER1):c.3019C>T (p.Gln1007Ter)
NC_000014.9:g.95105752G>A
CM000676.2:g.95105752G>A
NC_000014.8:g.95572089G>A
CM000676.1:g.95572089G>A
NC_000014.7:g.94641842G>A
NG_016311.1:g.56671C>T
ENST00000343455.8:c.3019C>T
ENST00000393063.6:c.3019C>T
ENST00000526495.6:c.3019C>T
ENST00000532939.3:c.3019C>T
ENST00000556045.6:c.3019C>T
ENST00000675540.1:n.841C>T
ENST00000675995.1:c.*1335C>T
ENST00000343455.7:c.3019C>T
ENST00000393063.5:c.3019C>T
ENST00000526495.5:c.3019C>T
ENST00000527414.5:c.3019C>T
ENST00000541352.5:c.3019C>T
ENST00000554367.1:n.228C>T
ENST00000556045.5:c.-211C>T
NM_001195573.1:c.3019C>T
NM_001271282.2:c.3019C>T
NM_001291628.1:c.3019C>T
NM_030621.4:c.3019C>T
NM_001271282.3:c.3019C>T
NM_001291628.2:c.3019C>T
NM_177438.3:c.3019C>T
NM_001395677.1:c.3019C>T
NM_001395678.1:c.3019C>T
NM_001395679.1:c.3019C>T
NM_001395680.1:c.3019C>T
NM_001395682.1:c.3019C>T
NM_001395683.1:c.3019C>T
NM_001395684.1:c.3019C>T
NM_001395685.1:c.3019C>T
NM_001395686.1:c.2737C>T
NM_001395687.1:c.2614C>T
NM_001395688.1:c.2614C>T
NM_001395689.1:c.2614C>T
NM_001395690.1:c.2614C>T
NM_001395691.1:c.2452C>T
NM_001395692.1:c.3019C>T
NM_001395693.1:c.3019C>T
NM_001395694.1:c.3019C>T
NM_001395695.1:c.3019C>T
NM_001395696.1:c.2614C>T
NM_001395697.1:c.1336C>T
NR_172715.1:n.3437C>T
NR_172716.1:n.3621C>T
NR_172717.1:n.3531C>T
NR_172718.1:n.3531C>T
NR_172719.1:n.3364C>T
NR_172720.1:n.3364C>T
NM_177438.3(DICER1):c.3019C>T (p.Gln1007Ter)
More

Pathogenic

Met criteria codes 4
PVS1 PP4 PM2_Supporting PS4_Supporting
Not Met criteria codes 14
PM1 PM5 PM6 BA1 BS4 BS3 BS1 BP2 BP4 PS2 PS3 PS1 PP1 PP3

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.3019C>T (p.Gln1007Ter) variant in DICER1 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 19/27 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 proband meeting DICER1 VCEP phenotype specificity scoring criteria (PS4_Supporting; PMID: 30178239, 28323992, 25118636, NCI). In addition, at least one patient with this variant was found to have a somatic second hit in a recognized DICER1 hotspot codon on tumor sequencing, which is highly specific for DICER1 syndrome (PP4, PMID: 28323992). 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, PP4, PM2_Supporting. (Bayesian Points: 11; VCEP specifications version 1; 02/11/2022).
Met criteria codes
PVS1
Nonsense variant upstream of residue 1850; predicted to undergo NMD
PP4
At least one patient with this variant was found to have a somatic second hit in a recognized DICER1 hotspot codon on tumor sequencing, which is highly specific for DICER1 syndrome (PP4, PMID: 28323992).
PM2_Supporting
Absent from gnomAD 2.1 (non-cancer) with >20x coverage in the region
PS4_Supporting
This variant received a total of 1 phenotype points for 1 proband meeting DICER1 VCEP phenotype specificity scoring criteria (PS4_Supporting; PMID: 30178239, 28323992, 25118636, NCI).
Not Met criteria codes
PM1
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
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
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
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
Two meioses. Insufficient to apply.
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
ClinGen Terms of Use.
¤ Powered by BCM's Genboree.