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.5248G>A (p.Val1750Ile)

CA390865129

477250 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e4597325-4969-4c96-bd6c-1436f48e57e3
Approved on: 2025-08-26
Published on: 2025-09-19

HGVS expressions

NM_177438.3:c.5248G>A
NM_177438.3(DICER1):c.5248G>A (p.Val1750Ile)
NC_000014.9:g.95094004C>T
CM000676.2:g.95094004C>T
NC_000014.8:g.95560341C>T
CM000676.1:g.95560341C>T
NC_000014.7:g.94630094C>T
NG_016311.1:g.68419G>A
ENST00000529720.2:c.5248G>A
ENST00000531162.7:c.5248G>A
ENST00000674628.2:c.5248G>A
ENST00000675540.2:c.*1898G>A
ENST00000696733.1:c.5248G>A
ENST00000696734.1:c.5248G>A
ENST00000696735.1:n.2235G>A
ENST00000696736.1:c.5248G>A
ENST00000696920.1:n.5511G>A
ENST00000696921.1:n.6354G>A
ENST00000696922.1:n.5657G>A
ENST00000696923.1:c.5248G>A
ENST00000696924.1:c.5248G>A
ENST00000696925.1:n.5657G>A
ENST00000343455.8:c.5248G>A
ENST00000393063.6:c.5248G>A
ENST00000526495.6:c.5248G>A
ENST00000556045.6:c.5248G>A
ENST00000675540.1:c.2993G>A
ENST00000675995.1:c.*3564G>A
ENST00000343455.7:c.5248G>A
ENST00000393063.5:c.5248G>A
ENST00000526495.5:c.5248G>A
ENST00000527414.5:c.5248G>A
ENST00000541352.5:c.5248G>A
ENST00000556045.5:c.1942G>A
NM_001195573.1:c.5248G>A
NM_001271282.2:c.5248G>A
NM_001291628.1:c.5248G>A
NM_030621.4:c.5248G>A
NM_177438.2:c.5248G>A
NM_001271282.3:c.5248G>A
NM_001291628.2:c.5248G>A
NM_001395677.1:c.5248G>A
NM_001395678.1:c.5248G>A
NM_001395679.1:c.5248G>A
NM_001395680.1:c.5248G>A
NM_001395682.1:c.5248G>A
NM_001395683.1:c.5248G>A
NM_001395684.1:c.5248G>A
NM_001395685.1:c.5248G>A
NM_001395686.1:c.4966G>A
NM_001395687.1:c.4843G>A
NM_001395688.1:c.4843G>A
NM_001395689.1:c.4843G>A
NM_001395690.1:c.4843G>A
NM_001395691.1:c.4681G>A
NM_001395697.1:c.3565G>A
NR_172715.1:n.5666G>A
NR_172716.1:n.5850G>A
NR_172717.1:n.5760G>A
NR_172718.1:n.5683G>A
NR_172719.1:n.5516G>A
NR_172720.1:n.5593G>A
More

Uncertain Significance

Met criteria codes 3
BP4 PM2_Supporting PM1_Supporting
Not Met criteria codes 14
BP2 PS1 PS3 PS4 PS2 PP4 PP1 PP3 PM5 BA1 BS3 BS4 BS1 BS2

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 1.4.0

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.5248G>A variant in DICER1 is a missense variant predicted to cause substitution of valine by isoleucine at amino acid 1750 (p.Val1750Ile). Although this variant has been observed in individuals undergoing genetic sequencing, to our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition (PS4 not met; Internal lab contributors). This variant has an allele frequency of 0.000001239 (2/1614128 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: 0.304; MaxEntScan and SpliceAI: no effect on splicing) (BP4). This variant resides within the RNase IIIb domain (PM1_Supporting; PMID: 31342592). 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: PM2_Supporting, BP4, PM1_Supporting. (Bayesian Points: 1; VCEP specifications version 1.4.0; 08/26/2025)
Met criteria codes
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.304; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
PM2_Supporting
This variant has an allele frequency of 0.000001239 (2/1614128alleles) 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).
PM1_Supporting
This variant resides within the RNase IIIb domain (PM1_Supporting; PMID: 31342592).
Not Met criteria codes
BP2
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
None identified.
PS4
Although this variant has been observed in individuals undergoing genetic sequencing, to our knowledge, this variant has not been reported in individuals with DICER1-related tumor predisposition (PS4 not met; Internal lab contributors).
PS2
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
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
None identified.
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
This variant has been seen in 3 unrelated females without tumors through age 50 in at least one testing laboratory (BS2 not met; Internal lab contributors).
Curation History
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