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.1453G>A (p.Gly485Arg)

CA265917282

477043 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 46c10a91-4249-41d8-be22-bb5f2aab0046
Approved on: 2024-10-22
Published on: 2024-11-13

HGVS expressions

NM_177438.3:c.1453G>A
NM_177438.3(DICER1):c.1453G>A (p.Gly485Arg)
NC_000014.9:g.95117678C>T
CM000676.2:g.95117678C>T
NC_000014.8:g.95584015C>T
CM000676.1:g.95584015C>T
NC_000014.7:g.94653768C>T
NG_016311.1:g.44745G>A
ENST00000529720.2:c.1453G>A
ENST00000531162.7:c.1453G>A
ENST00000674628.2:c.1453G>A
ENST00000675540.2:c.1453G>A
ENST00000696733.1:c.1453G>A
ENST00000696734.1:c.1453G>A
ENST00000696736.1:c.1453G>A
ENST00000696737.1:c.1453G>A
ENST00000696920.1:n.1716G>A
ENST00000696921.1:n.2559G>A
ENST00000696922.1:n.1862G>A
ENST00000696923.1:c.1453G>A
ENST00000696924.1:c.1453G>A
ENST00000696925.1:n.1862G>A
ENST00000696927.1:n.1056G>A
ENST00000696928.1:n.1650G>A
ENST00000343455.8:c.1453G>A
ENST00000393063.6:c.1453G>A
ENST00000526495.6:c.1453G>A
ENST00000532939.3:c.1453G>A
ENST00000556045.6:c.1453G>A
ENST00000674628.1:c.1453G>A
ENST00000675995.1:c.1453G>A
ENST00000343455.7:c.1453G>A
ENST00000393063.5:c.1453G>A
ENST00000526495.5:c.1453G>A
ENST00000527414.5:c.1453G>A
ENST00000532458.1:n.157G>A
ENST00000541352.5:c.1453G>A
NM_001195573.1:c.1453G>A
NM_001271282.2:c.1453G>A
NM_001291628.1:c.1453G>A
NM_030621.4:c.1453G>A
NM_177438.2:c.1453G>A
NM_001271282.3:c.1453G>A
NM_001291628.2:c.1453G>A
NM_001395677.1:c.1453G>A
NM_001395678.1:c.1453G>A
NM_001395679.1:c.1453G>A
NM_001395680.1:c.1453G>A
NM_001395682.1:c.1453G>A
NM_001395683.1:c.1453G>A
NM_001395684.1:c.1453G>A
NM_001395685.1:c.1453G>A
NM_001395686.1:c.1171G>A
NM_001395687.1:c.1048G>A
NM_001395688.1:c.1048G>A
NM_001395689.1:c.1048G>A
NM_001395690.1:c.1048G>A
NM_001395691.1:c.886G>A
NM_001395692.1:c.1453G>A
NM_001395693.1:c.1453G>A
NM_001395694.1:c.1453G>A
NM_001395695.1:c.1453G>A
NM_001395696.1:c.1048G>A
NM_001395697.1:c.-116G>A
NM_001395698.1:c.1048G>A
NR_172715.1:n.1871G>A
NR_172716.1:n.1798G>A
NR_172717.1:n.1965G>A
NR_172718.1:n.1965G>A
NR_172719.1:n.1798G>A
NR_172720.1:n.1798G>A
More

Uncertain Significance

Not Met criteria codes 8
BS1 BS2 BP4 BA1 PP3 PM1 PM5 PM2

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
The NM_177438.3:c.1453G>A variant in DICER1 is a missense variant predicted to cause substitution of glycine by arginine at amino acid 485 (p.Gly485Arg). To our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition. The total allele frequency in gnomAD v4.1.0 is 0.000007435 (12/1613916 alleles) with a highest population minor allele frequency of 0.00001017 (12/1179952 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.681, which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function (PP3 and BP4 not met). A different missense variant, c.1454G>A (p.Gly485Glu), in the same codon has been reported (ClinVar Variation ID: 2738880). However, this variant has not yet met the criteria to be classified as pathogenic by the ClinGen DICER VCEP (PM5 not met). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: no criteria met. (Bayesian Points: 0; VCEP specifications version 1.3.0; 10/22/2024)
Not Met criteria codes
BS1
The total allele frequency in gnomAD v4.1.0 is 0.000007435 (12/1613916 alleles) with a highest population minor allele frequency of 0.00001017 (12/1179952 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BS2
This variant has been seen in 4 unrelated females without tumors through age 50 in at least one testing laboratory, such that BS2_Supporting is not met. There were 24 total cases without DICER1-related phenotypes observed.
BP4
The computational predictor REVEL gives a score of 0.681, which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function (PP3 and BP4 not met).
BA1
The total allele frequency in gnomAD v4.1.0 is 0.000007435 (12/1613916 alleles) with a highest population minor allele frequency of 0.00001017 (12/1179952 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PP3
The computational predictor REVEL gives a score of 0.681, which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function (PP3 and BP4 not met).
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).
PM5
c.1454G>A (p.Gly485Glu) is VUS in ClinVar (ID: 2738880)
PM2
The total allele frequency in gnomAD v4.1.0 is 0.000007435 (12/1613916 alleles) with a highest population minor allele frequency of 0.00001017 (12/1179952 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
Curation History
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