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 label mismatch: DICER1 vs undefined
  • 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.5626G>A (p.Gly1876Arg)

CA7330608

429154 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 53fdeb29-ba34-4750-870d-ccfb1f262cce
Approved on: 2025-02-25
Published on: 2025-06-04

HGVS expressions

NM_177438.3:c.5626G>A
NM_177438.3(DICER1):c.5626G>A (p.Gly1876Arg)
NC_000014.9:g.95090641C>T
CM000676.2:g.95090641C>T
NC_000014.8:g.95556978C>T
CM000676.1:g.95556978C>T
NC_000014.7:g.94626731C>T
NG_016311.1:g.71782G>A
ENST00000529720.2:c.5626G>A
ENST00000531162.7:c.5626G>A
ENST00000674628.2:c.5626G>A
ENST00000675540.2:c.*2276G>A
ENST00000696733.1:c.*248G>A
ENST00000696734.1:c.*281G>A
ENST00000696735.1:n.2613G>A
ENST00000696736.1:c.*389G>A
ENST00000696920.1:n.5889G>A
ENST00000696921.1:n.6732G>A
ENST00000696922.1:n.8557G>A
ENST00000696923.1:c.*281G>A
ENST00000696924.1:c.*248G>A
ENST00000696925.1:n.8927G>A
ENST00000343455.8:c.5626G>A
ENST00000393063.6:c.5626G>A
ENST00000526495.6:c.5626G>A
ENST00000556045.6:c.*343G>A
ENST00000675540.1:c.3371G>A
ENST00000675995.1:c.*3942G>A
ENST00000343455.7:c.5626G>A
ENST00000393063.5:c.5626G>A
ENST00000526495.5:c.5626G>A
ENST00000527414.5:c.5626G>A
ENST00000527416.2:n.219G>A
ENST00000541352.5:c.5463G>A
ENST00000556045.5:c.2320G>A
NM_001195573.1:c.5463G>A
NM_001271282.2:c.5626G>A
NM_001291628.1:c.5626G>A
NM_030621.4:c.5626G>A
NM_177438.2:c.5626G>A
NM_001271282.3:c.5626G>A
NM_001291628.2:c.5626G>A
NM_001395677.1:c.5626G>A
NM_001395678.1:c.5626G>A
NM_001395679.1:c.5626G>A
NM_001395680.1:c.5626G>A
NM_001395682.1:c.5626G>A
NM_001395683.1:c.5626G>A
NM_001395684.1:c.5626G>A
NM_001395685.1:c.*172G>A
NM_001395686.1:c.5344G>A
NM_001395687.1:c.5221G>A
NM_001395688.1:c.5221G>A
NM_001395689.1:c.5221G>A
NM_001395690.1:c.5221G>A
NM_001395691.1:c.5059G>A
NM_001395697.1:c.3943G>A
NR_172715.1:n.6044G>A
NR_172716.1:n.6228G>A
NR_172717.1:n.6138G>A
NR_172718.1:n.6061G>A
NR_172719.1:n.5894G>A
NR_172720.1:n.6097G>A
More

Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 19
PM2 PM5 PM4 PM1 PVS1 BA1 BS2 BS4 BS3 BS1 BP7 BP2 PS2 PS1 PS3 PS4 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 1.3.0

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.5626G>A variant in DICER1 is a missense variant predicted to cause substitution of glycine by arginine at amino acid 1876 (p.Gly1876Arg). Although this variant has been observed in germline cases, to our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition (PS4 not met; Internal lab contributors). The total allele frequency in gnomAD v4.1.0 is 0.00001177 (19/1614002 alleles) with a highest population minor allele frequency of 0.0002343 (15/64030 alleles) in European (Finnish) population (PM2_Supporting, BS1, and BA1 are not met). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.41; MaxEntScan and SpliceAI: no effect on splicing) (BP4). In summary, this variant meets the criteria to be classified as Uncertain Significance for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4. (Bayesian Points: -1; VCEP specifications version 1.3.0; 02/25/2025)
Met criteria codes
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.41; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
Not Met criteria codes
PM2
The total allele frequency in gnomAD v4.1.0 is 0.00001177 (19/1614002alleles) with a highest population minor allele frequency of 0.0002343 (15/64030alleles) in European (Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PM5
The current variant is the only variant found in this codon in ClinVar.
PM4
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 critical functional domain by the ClinGen DICER1 VCEP (PM1 not met).
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
The total allele frequency in gnomAD v4.1.0 is 0.00001177 (19/1614002alleles) with a highest population minor allele frequency of 0.0002343 (15/64030alleles) in European (Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BS2
Unrelated females without tumors through age 50: Invitae: 5 Ambry: 3
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
The total allele frequency in gnomAD v4.1.0 is 0.00001177 (19/1614002alleles) with a highest population minor allele frequency of 0.0002343 (15/64030alleles) in European (Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
The current variant is the only variant found in this codon in ClinVar.
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Although this variant has been observed in germline cases, to our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition (PS4 not met; Internal lab contributors).
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
Curation History
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