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]
Link to SEPIO compliant JSON-LD document

Variant: NM_177438.2(DICER1):c.5104C>T (p.Gln1702Ter)

CA10586407

254344 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4aea1786-5074-47d4-8f93-4d157f9839e6
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.5104C>T
NM_177438.2(DICER1):c.5104C>T (p.Gln1702Ter)
NC_000014.9:g.95094148G>A
CM000676.2:g.95094148G>A
NC_000014.8:g.95560485G>A
CM000676.1:g.95560485G>A
NC_000014.7:g.94630238G>A
NG_016311.1:g.68275C>T
ENST00000343455.8:c.5104C>T
ENST00000393063.6:c.5104C>T
ENST00000526495.6:c.5104C>T
ENST00000556045.6:c.5104C>T
ENST00000675540.1:n.2849C>T
ENST00000675995.1:c.*3420C>T
ENST00000343455.7:c.5104C>T
ENST00000393063.5:c.5104C>T
ENST00000526495.5:c.5104C>T
ENST00000527414.5:c.5104C>T
ENST00000541352.5:c.5104C>T
ENST00000556045.5:c.1798C>T
NM_001195573.1:c.5104C>T
NM_001271282.2:c.5104C>T
NM_001291628.1:c.5104C>T
NM_030621.4:c.5104C>T
NM_001271282.3:c.5104C>T
NM_001291628.2:c.5104C>T
NM_177438.3:c.5104C>T
NM_001395677.1:c.5104C>T
NM_001395678.1:c.5104C>T
NM_001395679.1:c.5104C>T
NM_001395680.1:c.5104C>T
NM_001395682.1:c.5104C>T
NM_001395683.1:c.5104C>T
NM_001395684.1:c.5104C>T
NM_001395685.1:c.5104C>T
NM_001395686.1:c.4822C>T
NM_001395687.1:c.4699C>T
NM_001395688.1:c.4699C>T
NM_001395689.1:c.4699C>T
NM_001395690.1:c.4699C>T
NM_001395691.1:c.4537C>T
NM_001395697.1:c.3421C>T
NR_172715.1:n.5522C>T
NR_172716.1:n.5706C>T
NR_172717.1:n.5616C>T
NR_172718.1:n.5539C>T
NR_172719.1:n.5372C>T
NR_172720.1:n.5449C>T
NM_177438.3(DICER1):c.5104C>T (p.Gln1702Ter)

Pathogenic

Met criteria codes 3
PS4_Supporting PM2_Supporting PVS1
Not Met criteria codes 10
BS4 BS3 BS1 BP2 BA1 PS2 PS3 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.5104C>T (p.Gln1702Ter) variant in DICER1 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 24/27 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 family meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; PMID: 22157934, 22180160, 26925222). This variant is absent from gnomAD non-cancer dataset v2.1.1 and v3.1.1 (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, PM2_supporting, PS4_supporting. (Bayesian Points: 10; VCEP specifications version 1; 02/11/2022)
Met criteria codes
PS4_Supporting
Germline in a F with cervical rhabdomyosarcoma and PPB Type Ir diagnosed age 9; SLCT age 13; thyroid nodules age 14. Mother (carrier): SCC of cervix age 28 and basal cell carcinoma of skin age 35. (ALL SAME CASE: NCI, Invitae, PMID: 22157934, 22180160, 26925222): 1 point
PM2_Supporting
Absent in gnomAD
PVS1
Predicted to undergo NMD (stop codon 5’ of p.P1850 in relevant transcript)
Not Met criteria codes
BS4
Not met
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Absent in gnomAD
BP2
Not observed
BA1
Absent in gnomAD
PS2
No de novo cases in internal data or literature
PS3
Do not apply as PVS1 is applied at full strength
PP1
No reported families segregating disease
PM6
No de novo cases in internal data or literature
PM1
Putative variant in Rnase IIIb domain – but rules specify missense variant so not applied
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