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.5729G>A (p.Arg1910Gln)

CA390863032

825925 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: b499c2a0-98c0-4af5-ac6f-f993a7c3d9cc
Approved on: 2024-10-22
Published on: 2024-11-13

HGVS expressions

NM_177438.3:c.5729G>A
NM_177438.3(DICER1):c.5729G>A (p.Arg1910Gln)
NC_000014.9:g.95090538C>T
CM000676.2:g.95090538C>T
NC_000014.8:g.95556875C>T
CM000676.1:g.95556875C>T
NC_000014.7:g.94626628C>T
NG_016311.1:g.71885G>A
ENST00000529720.2:c.5729G>A
ENST00000531162.7:c.5729G>A
ENST00000674628.2:c.5729G>A
ENST00000675540.2:c.*2379G>A
ENST00000696733.1:c.*351G>A
ENST00000696734.1:c.*384G>A
ENST00000696735.1:n.2716G>A
ENST00000696736.1:c.*492G>A
ENST00000696920.1:n.5992G>A
ENST00000696921.1:n.6835G>A
ENST00000696922.1:n.8660G>A
ENST00000696923.1:c.*384G>A
ENST00000696924.1:c.*351G>A
ENST00000696925.1:n.9030G>A
ENST00000343455.8:c.5729G>A
ENST00000393063.6:c.5729G>A
ENST00000526495.6:c.5729G>A
ENST00000556045.6:c.*446G>A
ENST00000675540.1:c.3474G>A
ENST00000675995.1:c.*4045G>A
ENST00000343455.7:c.5729G>A
ENST00000393063.5:c.5729G>A
ENST00000526495.5:c.5729G>A
ENST00000527414.5:c.5729G>A
ENST00000527416.2:n.322G>A
ENST00000541352.5:c.*76G>A
ENST00000556045.5:c.2423G>A
NM_001195573.1:c.*76G>A
NM_001271282.2:c.5729G>A
NM_001291628.1:c.5729G>A
NM_030621.4:c.5729G>A
NM_177438.2:c.5729G>A
NM_001271282.3:c.5729G>A
NM_001291628.2:c.5729G>A
NM_001395677.1:c.5729G>A
NM_001395678.1:c.5729G>A
NM_001395679.1:c.5729G>A
NM_001395680.1:c.5729G>A
NM_001395682.1:c.5729G>A
NM_001395683.1:c.5729G>A
NM_001395684.1:c.5729G>A
NM_001395685.1:c.*275G>A
NM_001395686.1:c.5447G>A
NM_001395687.1:c.5324G>A
NM_001395688.1:c.5324G>A
NM_001395689.1:c.5324G>A
NM_001395690.1:c.5324G>A
NM_001395691.1:c.5162G>A
NM_001395697.1:c.4046G>A
NR_172715.1:n.6147G>A
NR_172716.1:n.6331G>A
NR_172717.1:n.6241G>A
NR_172718.1:n.6164G>A
NR_172719.1:n.5997G>A
NR_172720.1:n.6200G>A
More

Uncertain Significance

Met criteria codes 2
PM2_Supporting BP4
Not Met criteria codes 19
PM6 PM1 PM4 PM5 BA1 BS3 BS4 BS1 BS2 BP7 BP2 PVS1 PS2 PS3 PS1 PS4 PP1 PP4 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 1.3.0

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.5729G>A variant in DICER1 is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 1910 (p.Arg1910Gln). This variant has an allele frequency of 0.0000006196 (1/1614038 alleles) across gnomAD v4.1.0 with no more than one allele in any subpopulation, which is lower than the ClinGen DICER1 VCEP threshold (<0.000005) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.29; MaxEntScan and SpliceAI: no effect on splicing) (BP4). In summary, this variant meets the criteria to be classified as uncertain significance for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PM2_Supporting, BP4. (Bayesian Points: 0; VCEP specifications version 1.1.3; 10/22/2024)
Met criteria codes
PM2_Supporting
This variant has an allele frequency of 6.196e-7 (1/1614038 alleles) across gnomAD v4.1.0 with no more than one allele in any subpopulation, which is lower than the ClinGen DICER1 VCEP threshold (<0.000005) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.29; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
Not Met criteria codes
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
This variant does not reside within a region of the RNAse IIIb domain that is defined as a mutational hotspot or critical functional domain by the ClinGen DICER1 VCEP (PM1 not met).
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
Another missense variant [c.5729G>C, p.Arg1910Pro] in the same codon has been reported [ClinVar Variation ID: 477269]. However, this variant has not yet met the criteria to be classified as pathogenic by the ClinGen DICER1 VCEP (PM5 not met).
BA1
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
BS4
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
BS2
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
PVS1
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
PS4
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
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
Curation History
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