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.1157A>G (p.Lys386Arg)

CA7331519

479632 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 79f74ab3-10d3-48d5-a988-da81ddd85169
Approved on: 2024-08-27
Published on: 2024-09-16

HGVS expressions

NM_177438.3:c.1157A>G
NM_177438.3(DICER1):c.1157A>G (p.Lys386Arg)
NC_000014.9:g.95124415T>C
CM000676.2:g.95124415T>C
NC_000014.8:g.95590752T>C
CM000676.1:g.95590752T>C
NC_000014.7:g.94660505T>C
NG_016311.1:g.38008A>G
ENST00000529720.2:c.1157A>G
ENST00000531162.7:c.1157A>G
ENST00000674628.2:c.1157A>G
ENST00000675540.2:c.1157A>G
ENST00000696733.1:c.1157A>G
ENST00000696734.1:c.1157A>G
ENST00000696736.1:c.1157A>G
ENST00000696737.1:c.1157A>G
ENST00000696921.1:n.2263A>G
ENST00000696922.1:n.1566A>G
ENST00000696923.1:c.1157A>G
ENST00000696924.1:c.1157A>G
ENST00000696925.1:n.1566A>G
ENST00000696927.1:n.760A>G
ENST00000696928.1:n.1354A>G
ENST00000343455.8:c.1157A>G
ENST00000393063.6:c.1157A>G
ENST00000526495.6:c.1157A>G
ENST00000532939.3:c.1157A>G
ENST00000556045.6:c.1157A>G
ENST00000674628.1:c.1157A>G
ENST00000675995.1:c.1157A>G
ENST00000343455.7:c.1157A>G
ENST00000393063.5:c.1157A>G
ENST00000526495.5:c.1157A>G
ENST00000527414.5:c.1157A>G
ENST00000541352.5:c.1157A>G
NM_001195573.1:c.1157A>G
NM_001271282.2:c.1157A>G
NM_001291628.1:c.1157A>G
NM_030621.4:c.1157A>G
NM_177438.2:c.1157A>G
NM_001271282.3:c.1157A>G
NM_001291628.2:c.1157A>G
NM_001395677.1:c.1157A>G
NM_001395678.1:c.1157A>G
NM_001395679.1:c.1157A>G
NM_001395680.1:c.1157A>G
NM_001395682.1:c.1157A>G
NM_001395683.1:c.1157A>G
NM_001395684.1:c.1157A>G
NM_001395685.1:c.1157A>G
NM_001395686.1:c.875A>G
NM_001395687.1:c.752A>G
NM_001395688.1:c.752A>G
NM_001395689.1:c.752A>G
NM_001395690.1:c.752A>G
NM_001395691.1:c.590A>G
NM_001395692.1:c.1157A>G
NM_001395693.1:c.1157A>G
NM_001395694.1:c.1157A>G
NM_001395695.1:c.1157A>G
NM_001395696.1:c.752A>G
NM_001395697.1:c.-412A>G
NM_001395698.1:c.752A>G
NM_001395699.1:c.1157A>G
NM_001395700.1:c.1157A>G
NR_172715.1:n.1371A>G
NR_172716.1:n.1502A>G
NR_172717.1:n.1669A>G
NR_172718.1:n.1669A>G
NR_172719.1:n.1502A>G
NR_172720.1:n.1502A>G
More

Likely Benign

Met criteria codes 3
BP2 BP4 BS2_Supporting
Not Met criteria codes 23
PVS1 BS4 BS3 BS1 BP3 BP1 BP5 BP7 PS1 PS4 PS3 PS2 BA1 PP4 PP1 PP3 PP2 PM5 PM1 PM3 PM4 PM6 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.1157A>G variant in DICER1 is a missense variant predicted to cause substitution of lysine by arginine at amino acid 386 (p.Lys386Arg). This variant has been observed in trans with the variant c.3091C>T, p.Gln1031Ter (Internal lab contributors) which would be classified as pathogenic/likely pathogenic by the ClinGen DICER1 VCEP specifications (BP2). This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors). The total allele frequency in gnomAD v4.1.0 is 0.00001053 (17/1614068 alleles) with a highest population minor allele frequency of 0.00001356 (16/1180004 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.123; MaxEntScan and SpliceAI: no effect on splicing) (BP4). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2_supporting, BP2, BP4. (Bayesian Points: -3; VCEP specifications version 1.3.0; 08/27/2024)
Met criteria codes
BP2
This variant has been observed in trans with the variant c.3091C>T, p.Gln1031Ter (Internal lab contributors) which would be classified as pathogenic/likely pathogenic by the ClinGen DICER1 VCEP specifications (BP2).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.123; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
BS2_Supporting
This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors).
Not Met criteria codes
PVS1
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
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 0.00001053 (17/1614068 alleles) with a highest population minor allele frequency of 0.00001356 (16/1180004 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
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
PS2
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 0.00001053 (17/1614068 alleles) with a highest population minor allele frequency of 0.00001356 (16/1180004 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
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
PP2
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
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The total allele frequency in gnomAD v4.1.0 is 0.00001053 (17/1614068 alleles) with a highest population minor allele frequency of 0.00001356 (16/1180004 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
Curation History
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