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 computer assertion could be determined for this classification!

Variant: NM_177438.3(DICER1):c.527A>T (p.Glu176Val)

CA7331646

543562 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 52f4a764-e8cc-49b7-9d64-3d5d19e39c3b
Approved on: 2024-02-27
Published on: 2024-05-08

HGVS expressions

NM_177438.3:c.527A>T
NM_177438.3(DICER1):c.527A>T (p.Glu176Val)
NC_000014.9:g.95130104T>A
CM000676.2:g.95130104T>A
NC_000014.8:g.95596441T>A
CM000676.1:g.95596441T>A
NC_000014.7:g.94666194T>A
NG_016311.1:g.32319A>T
ENST00000529720.2:c.527A>T
ENST00000531162.7:c.527A>T
ENST00000674628.2:c.527A>T
ENST00000675540.2:c.527A>T
ENST00000696733.1:c.527A>T
ENST00000696734.1:c.527A>T
ENST00000696736.1:c.527A>T
ENST00000696737.1:c.527A>T
ENST00000696921.1:n.1633A>T
ENST00000696922.1:n.936A>T
ENST00000696923.1:c.527A>T
ENST00000696924.1:c.527A>T
ENST00000696925.1:n.936A>T
ENST00000696927.1:n.130A>T
ENST00000696928.1:n.724A>T
ENST00000343455.8:c.527A>T
ENST00000393063.6:c.527A>T
ENST00000526495.6:c.527A>T
ENST00000532939.3:c.527A>T
ENST00000556045.6:c.527A>T
ENST00000674628.1:c.527A>T
ENST00000675995.1:c.527A>T
ENST00000343455.7:c.527A>T
ENST00000393063.5:c.527A>T
ENST00000526495.5:c.527A>T
ENST00000527414.5:c.527A>T
ENST00000529206.1:n.668A>T
ENST00000541352.5:c.527A>T
NM_001195573.1:c.527A>T
NM_001271282.2:c.527A>T
NM_001291628.1:c.527A>T
NM_030621.4:c.527A>T
NM_177438.2:c.527A>T
NM_001271282.3:c.527A>T
NM_001291628.2:c.527A>T
NM_001395677.1:c.527A>T
NM_001395678.1:c.527A>T
NM_001395679.1:c.527A>T
NM_001395680.1:c.527A>T
NM_001395682.1:c.527A>T
NM_001395683.1:c.527A>T
NM_001395684.1:c.527A>T
NM_001395685.1:c.527A>T
NM_001395686.1:c.245A>T
NM_001395687.1:c.122A>T
NM_001395688.1:c.122A>T
NM_001395689.1:c.122A>T
NM_001395690.1:c.122A>T
NM_001395691.1:c.-20-21A>T
NM_001395692.1:c.527A>T
NM_001395693.1:c.527A>T
NM_001395694.1:c.527A>T
NM_001395695.1:c.527A>T
NM_001395696.1:c.122A>T
NM_001395697.1:c.-1042A>T
NM_001395698.1:c.122A>T
NM_001395699.1:c.527A>T
NM_001395700.1:c.527A>T
NR_172715.1:n.741A>T
NR_172716.1:n.872A>T
NR_172717.1:n.1039A>T
NR_172718.1:n.1039A>T
NR_172719.1:n.872A>T
NR_172720.1:n.872A>T
More

Uncertain Significance

Met criteria codes 1
PP3
Not Met criteria codes 19
PS3 PS2 PS4 PS1 BA1 PP4 PP1 PM2 PM1 PM5 PM4 PVS1 BS3 BS4 BS1 BS2 BP7 BP2 BP4

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_177438.2:c.527A>T variant in DICER1 is a missense variant predicted to cause substitution of glutamic acid by valine at amino acid 176 (p.Glu176Val). The highest population minor allele frequency in gnomAD v4.1.0 is 0.000001695 (2/1179702 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). In silico tools predict damaging impact of the variant on protein function (REVEL: 0.835) (PP3). 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: PP3. (Bayesian Points: 1; VCEP specifications version 1.3.0; 02/27/2024)
Met criteria codes
PP3
In silico tools predict damaging impact of the variant on protein function (REVEL: 0.835) (PP3).
Not Met criteria codes
PS3
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
PS4
This variant received a total of 0 phenotype points across 15 unrelated probands. (PS4 not met; Internal lab contributors).
PS1
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
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
PM2
The highest population minor allele frequency in gnomAD v4.1.0 is 0.000004786 (2/417908 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are 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
2 different missense variants, c.526G>C (p.Glu176Gln) and c.526G>A (p.Glu176Lys), in the same codon have been reported (ClinVar Variation IDs 2129178, 642431). However, these variants have not yet met the criteria to be classified as pathogenic by the ClinGen DICER VCEP (PM5 not met).
PM4
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
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
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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