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_177438.3(DICER1):c.4283T>A (p.Met1428Lys)

CA16614307

412118 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 60b17876-0c88-4365-95e6-1bacb22ce279
Approved on: 2024-01-09
Published on: 2024-01-17

HGVS expressions

NM_177438.3:c.4283T>A
NM_177438.3(DICER1):c.4283T>A (p.Met1428Lys)
NC_000014.9:g.95096637A>T
CM000676.2:g.95096637A>T
NC_000014.8:g.95562974A>T
CM000676.1:g.95562974A>T
NC_000014.7:g.94632727A>T
NG_016311.1:g.65786T>A
ENST00000343455.8:c.4283T>A
ENST00000393063.6:c.4283T>A
ENST00000526495.6:c.4283T>A
ENST00000532939.3:c.4283T>A
ENST00000556045.6:c.4283T>A
ENST00000675540.1:c.2028T>A
ENST00000675995.1:c.*2599T>A
ENST00000343455.7:c.4283T>A
ENST00000393063.5:c.4283T>A
ENST00000526495.5:c.4283T>A
ENST00000527414.5:c.4283T>A
ENST00000532939.2:c.318T>A
ENST00000541352.5:c.4283T>A
ENST00000556045.5:c.977T>A
NM_001195573.1:c.4283T>A
NM_001271282.2:c.4283T>A
NM_001291628.1:c.4283T>A
NM_030621.4:c.4283T>A
NM_177438.2:c.4283T>A
NM_001271282.3:c.4283T>A
NM_001291628.2:c.4283T>A
NM_001395677.1:c.4283T>A
NM_001395678.1:c.4283T>A
NM_001395679.1:c.4283T>A
NM_001395680.1:c.4283T>A
NM_001395682.1:c.4283T>A
NM_001395683.1:c.4283T>A
NM_001395684.1:c.4283T>A
NM_001395685.1:c.4283T>A
NM_001395686.1:c.4001T>A
NM_001395687.1:c.3878T>A
NM_001395688.1:c.3878T>A
NM_001395689.1:c.3878T>A
NM_001395690.1:c.3878T>A
NM_001395691.1:c.3716T>A
NM_001395692.1:c.4283T>A
NM_001395693.1:c.4283T>A
NM_001395694.1:c.4283T>A
NM_001395695.1:c.4283T>A
NM_001395696.1:c.3878T>A
NM_001395697.1:c.2600T>A
NR_172715.1:n.4701T>A
NR_172716.1:n.4885T>A
NR_172717.1:n.4795T>A
NR_172718.1:n.4718T>A
NR_172719.1:n.4551T>A
NR_172720.1:n.4628T>A

Likely Benign

Met criteria codes 2
BP4 BS2_Supporting
Not Met criteria codes 19
PM2 PM3 PM1 PM4 PM5 BA1 PVS1 BS4 BS3 BS1 PS4 PS3 PS1 BP7 BP2 BP3 PP4 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 1.2.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
DICER1 and miRNA-Processing Gene VCEP
NM_177438.3(DICER1):c.4283T>A variant in DICER1 is a missense variant predicted to cause substitution of methionine by lysine at amino acid 1428 (p.Met1802Lys). This variant received a total of 0.5 phenotype points in a single proband (PS4 not met; Internal lab contributors SCV001509541.1). This variant has also been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors SCV001509541.1, SCV001444307.1). The highest population minor allele frequency in gnomAD v2.1.1 non-cancer is 0.00008606 (3/34860 alleles) in Latino/Admixed American population (PM2_Supporting, BS1, and BA1 are not met). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.115; MaxEntScan and SpliceAI: no effect on splicing) (BP4). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2_Supporting, BP4. (Bayesian Points: -2; VCEP specifications version 1.2.0; 01/09/2024)
Met criteria codes
BP4
REVEL 0.115 (<0.5) and no splicing predicted
BS2_Supporting
10+ unrelated females from a single source have reached age 50 without a tumor diagnosis
Not Met criteria codes
PM2
3/34860 (0.008606%) Latino/Admixed American (gnomad 2.1.1 non-cancer). 2/64806 (0.003086%) European (non-Finnish) (gnomad 3.1.2. non-cancers)
PM3
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
PM4
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
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
PS4
1 case with moderate specificity (0.5pts)
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
BP7
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
BP3
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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