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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_177438.3(DICER1):c.5516G>A (p.Arg1839Gln)

CA158288

133976 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c2244761-5cda-4ad6-97d6-89d93ef19819
Approved on: 2023-04-25
Published on: 2023-05-12

HGVS expressions

NM_177438.3:c.5516G>A
NM_177438.3(DICER1):c.5516G>A (p.Arg1839Gln)
NC_000014.9:g.95091214C>T
CM000676.2:g.95091214C>T
NC_000014.8:g.95557551C>T
CM000676.1:g.95557551C>T
NC_000014.7:g.94627304C>T
NG_016311.1:g.71209G>A
ENST00000529720.2:c.5516G>A
ENST00000531162.7:c.5516G>A
ENST00000674628.2:c.5516G>A
ENST00000675540.2:c.*2166G>A
ENST00000696733.1:c.*138G>A
ENST00000696734.1:c.*171G>A
ENST00000696735.1:n.2503G>A
ENST00000696736.1:c.5516G>A
ENST00000696920.1:n.5779G>A
ENST00000696921.1:n.6622G>A
ENST00000696922.1:n.8447G>A
ENST00000696923.1:c.*171G>A
ENST00000696924.1:c.*138G>A
ENST00000696925.1:n.8447G>A
ENST00000343455.8:c.5516G>A
ENST00000393063.6:c.5516G>A
ENST00000526495.6:c.5516G>A
ENST00000556045.6:c.*233G>A
ENST00000675540.1:c.3261G>A
ENST00000675995.1:c.*3832G>A
ENST00000343455.7:c.5516G>A
ENST00000393063.5:c.5516G>A
ENST00000526495.5:c.5516G>A
ENST00000527414.5:c.5516G>A
ENST00000527416.2:n.109G>A
ENST00000527554.2:n.209G>A
ENST00000541352.5:c.5365-105G>A
ENST00000556045.5:c.2210G>A
NM_001195573.1:c.5365-105G>A
NM_001271282.2:c.5516G>A
NM_001291628.1:c.5516G>A
NM_030621.4:c.5516G>A
NM_177438.2:c.5516G>A
NM_001271282.3:c.5516G>A
NM_001291628.2:c.5516G>A
NM_001395677.1:c.5516G>A
NM_001395678.1:c.5516G>A
NM_001395679.1:c.5516G>A
NM_001395680.1:c.5516G>A
NM_001395682.1:c.5516G>A
NM_001395683.1:c.5516G>A
NM_001395684.1:c.5516G>A
NM_001395685.1:c.5516G>A
NM_001395686.1:c.5234G>A
NM_001395687.1:c.5111G>A
NM_001395688.1:c.5111G>A
NM_001395689.1:c.5111G>A
NM_001395690.1:c.5111G>A
NM_001395691.1:c.4949G>A
NM_001395697.1:c.3833G>A
NR_172715.1:n.5934G>A
NR_172716.1:n.6118G>A
NR_172717.1:n.6028G>A
NR_172718.1:n.5951G>A
NR_172719.1:n.5784G>A
NR_172720.1:n.5987G>A
More

Uncertain Significance

Met criteria codes 3
PM1_Supporting BP4 BS2_Supporting
Not Met criteria codes 17
PP1 PP3 PP4 PM2 PS1 PS2 PS3 PS4 PM5 PM4 BA1 PVS1 BP7 BP2 BS1 BS4 BS3

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 1.1.0

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.5516G>A variant in DICER1 is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 1839 (p.Arg1839Gln). This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors: Invitae; Ambry). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006196 (8/129108 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). This variant resides within the RNase IIIb domain of DICER1, a mutational hotspot domain with critical functional as defined by the ClinGen DICER1 VCEP (PM1_Supporting; PMID: 31342592). The computational predictor REVEL gives a score of 0.234, 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). Due to conflicting evidence, this variant is classified as a variant of unknown significance for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2_Supporting, PM1_Supporting, BP4. (Bayesian Points: -1; VCEP specifications version 1.1.0; 04/25/2023)
Met criteria codes
PM1_Supporting
This variant resides within the RNase IIIb domain of DICER1, a mutational hotspot domain with critical functional as defined by the ClinGen DICER1 VCEP (PM1_Supporting; PMID: 31342592).
BP4
The computational predictor REVEL gives a score of 0.234, 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).
BS2_Supporting
This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors: Invitae; Ambry).
Not Met criteria codes
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006196 (8/129108 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PS1
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
PS4
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
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006196 (8/129108 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PVS1
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
BS1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006196 (8/129108 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
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
Curation History
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