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.59C>T (p.Ala20Val)

CA332140

133964 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c125e21b-58b1-464c-9b3e-4a627e10bf8a
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.59C>T
NM_177438.2(DICER1):c.59C>T (p.Ala20Val)
NC_000014.9:g.95133400G>A
CM000676.2:g.95133400G>A
NC_000014.8:g.95599737G>A
CM000676.1:g.95599737G>A
NC_000014.7:g.94669490G>A
NG_016311.1:g.29023C>T
ENST00000343455.8:c.59C>T
ENST00000393063.6:c.59C>T
ENST00000526495.6:c.59C>T
ENST00000531162.6:c.59C>T
ENST00000532939.3:c.59C>T
ENST00000556045.6:c.59C>T
ENST00000674628.1:c.59C>T
ENST00000675995.1:c.59C>T
ENST00000343455.7:c.59C>T
ENST00000393063.5:c.59C>T
ENST00000526495.5:c.59C>T
ENST00000527414.5:c.59C>T
ENST00000529206.1:n.200C>T
ENST00000529720.1:c.59C>T
ENST00000531162.5:c.59C>T
ENST00000541352.5:c.59C>T
NM_001195573.1:c.59C>T
NM_001271282.2:c.59C>T
NM_001291628.1:c.59C>T
NM_030621.4:c.59C>T
NM_001271282.3:c.59C>T
NM_001291628.2:c.59C>T
NM_177438.3:c.59C>T
NM_001395677.1:c.59C>T
NM_001395678.1:c.59C>T
NM_001395679.1:c.59C>T
NM_001395680.1:c.59C>T
NM_001395682.1:c.59C>T
NM_001395683.1:c.59C>T
NM_001395684.1:c.59C>T
NM_001395685.1:c.59C>T
NM_001395686.1:c.-216C>T
NM_001395687.1:c.-130-723C>T
NM_001395688.1:c.-216C>T
NM_001395689.1:c.-216C>T
NM_001395690.1:c.-216C>T
NM_001395691.1:c.-400C>T
NM_001395692.1:c.59C>T
NM_001395693.1:c.59C>T
NM_001395694.1:c.59C>T
NM_001395695.1:c.59C>T
NM_001395696.1:c.-216C>T
NM_001395697.1:c.-1510C>T
NM_001395698.1:c.-216C>T
NM_001395699.1:c.59C>T
NM_001395700.1:c.59C>T
NR_172715.1:n.404C>T
NR_172716.1:n.404C>T
NR_172717.1:n.571C>T
NR_172718.1:n.571C>T
NR_172719.1:n.404C>T
NR_172720.1:n.404C>T
NM_177438.3(DICER1):c.59C>T (p.Ala20Val)
More

Benign

Met criteria codes 3
BS2 BS1 BP4
Not Met criteria codes 15
PS2 PS4 PS1 PS3 BA1 PP1 PP4 PP3 PM5 PM1 PM6 PM2 BS4 BS3 BP2

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.59C>T is a missense variant in DICER1 predicted to cause substitution of Alanine by Valine at amino acid 20 (p.Ala20Val). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0009673 in the non-Finnish European population, which is higher than the ClinGen DICER1 VCEP threshold (>0.0003) for BS1, and therefore meets this criterion (BS1). This variant has been observed in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (Internal lab contributors GTRs: 61756, 500031) and has been observed in a homozygous state in 3 healthy individuals (Internal lab contributors GTR: 500031)(BS2). The computational predictor REVEL gives a score of 0.302, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS1, BS2, BP4. (Bayesian Points: -9; VCEP specifications version 1; 02/11/2022).
Met criteria codes
BS2
This variant has been observed in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (Internal lab contributors: 61756, 500031) and has been observed in a homozygous state in 3 healthy individuals (Internal lab contributors: 500031)(BS2).
BS1
0.09673% in NFE in gnomAD v2.1.1 (non-cancer)
BP4
REVEL score = 0.302
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
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
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
0.3453% in AJ pop in gnomAD v2.1.1 (non-cancer) – Founder pop therefore N/A
PP1
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
PP3
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
PM1
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
PM2
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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