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 computer assertion could be determined for this classification!


Variant: NM_177438.3(DICER1):c.1381A>G (p.Ile461Val)

CA7331487

242037 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
UUID: b2f3ef09-1952-4eac-85bb-bcf6bc2eb97d
Approved on: 2024-06-25
Published on: 2024-07-30

HGVS expressions

NM_177438.3:c.1381A>G
NM_177438.3(DICER1):c.1381A>G (p.Ile461Val)
NC_000014.9:g.95117750T>C
CM000676.2:g.95117750T>C
NC_000014.8:g.95584087T>C
CM000676.1:g.95584087T>C
NC_000014.7:g.94653840T>C
NG_016311.1:g.44673A>G
ENST00000529720.2:c.1381A>G
ENST00000531162.7:c.1381A>G
ENST00000674628.2:c.1381A>G
ENST00000675540.2:c.1381A>G
ENST00000696733.1:c.1381A>G
ENST00000696734.1:c.1381A>G
ENST00000696736.1:c.1381A>G
ENST00000696737.1:c.1381A>G
ENST00000696920.1:n.1644A>G
ENST00000696921.1:n.2487A>G
ENST00000696922.1:n.1790A>G
ENST00000696923.1:c.1381A>G
ENST00000696924.1:c.1381A>G
ENST00000696925.1:n.1790A>G
ENST00000696927.1:n.984A>G
ENST00000696928.1:n.1578A>G
ENST00000343455.8:c.1381A>G
ENST00000393063.6:c.1381A>G
ENST00000526495.6:c.1381A>G
ENST00000532939.3:c.1381A>G
ENST00000556045.6:c.1381A>G
ENST00000674628.1:c.1381A>G
ENST00000675995.1:c.1381A>G
ENST00000343455.7:c.1381A>G
ENST00000393063.5:c.1381A>G
ENST00000526495.5:c.1381A>G
ENST00000527414.5:c.1381A>G
ENST00000532458.1:n.85A>G
ENST00000541352.5:c.1381A>G
NM_001195573.1:c.1381A>G
NM_001271282.2:c.1381A>G
NM_001291628.1:c.1381A>G
NM_030621.4:c.1381A>G
NM_177438.2:c.1381A>G
NM_001271282.3:c.1381A>G
NM_001291628.2:c.1381A>G
NM_001395677.1:c.1381A>G
NM_001395678.1:c.1381A>G
NM_001395679.1:c.1381A>G
NM_001395680.1:c.1381A>G
NM_001395682.1:c.1381A>G
NM_001395683.1:c.1381A>G
NM_001395684.1:c.1381A>G
NM_001395685.1:c.1381A>G
NM_001395686.1:c.1099A>G
NM_001395687.1:c.976A>G
NM_001395688.1:c.976A>G
NM_001395689.1:c.976A>G
NM_001395690.1:c.976A>G
NM_001395691.1:c.814A>G
NM_001395692.1:c.1381A>G
NM_001395693.1:c.1381A>G
NM_001395694.1:c.1381A>G
NM_001395695.1:c.1381A>G
NM_001395696.1:c.976A>G
NM_001395697.1:c.-188A>G
NM_001395698.1:c.976A>G
NR_172715.1:n.1799A>G
NR_172716.1:n.1726A>G
NR_172717.1:n.1893A>G
NR_172718.1:n.1893A>G
NR_172719.1:n.1726A>G
NR_172720.1:n.1726A>G
More

Benign

Met criteria codes 3
BS2 BP4 BA1
Not Met criteria codes 16
BS4 BS3 BS1 BP7 BP2 PS2 PS3 PS1 PP4 PP1 PP3 PM2 PM1 PM4 PM5 PVS1

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.1381A>G variant in DICER1 is a missense variant predicted to cause substitution of isoleucine by valine at amino acid 461 (p.Ile461Val). The highest population minor allele frequency in gnomAD v4.1.0 is 0.005261 (32/6082 alleles) in the Middle Eastern population, which is higher than the ClinGen DICER1 VCEP threshold (>0.003) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BA1. (Bayesian Points: NA; VCEP specifications version 1.3.0; 06/25/2024)
Met criteria codes
BS2
This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (Internal lab contributors) and has been observed in a homozygous state in 4 healthy individuals (Internal lab contributors) (BS2).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.286; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
BA1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.005261 (32/6082 alleles) in the Middle Eastern population, which is higher than the ClinGen DICER1 VCEP threshold (>0.003) for BA1, and therefore meets this criterion (BA1).
Not Met criteria codes
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
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
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
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
PM2
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
2 different missense variants, c.1383A>G (p.Ile461Met) and c.1381A>T (p.Ile461Leu), in the same codon have been reported (ClinVar Variation IDs 863501, 485533). However, these variants have not yet met the criteria to be classified as pathogenic by the ClinGen DICER VCEP (PM5 not met).
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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