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.1168T>C (p.Tyr390His)

CA10583221

242033 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 6b549a8c-b449-4013-8397-ed65594f4d67
Approved on: 2024-08-27
Published on: 2024-09-16

HGVS expressions

NM_177438.3:c.1168T>C
NM_177438.3(DICER1):c.1168T>C (p.Tyr390His)
NC_000014.9:g.95124404A>G
CM000676.2:g.95124404A>G
NC_000014.8:g.95590741A>G
CM000676.1:g.95590741A>G
NC_000014.7:g.94660494A>G
NG_016311.1:g.38019T>C
ENST00000529720.2:c.1168T>C
ENST00000531162.7:c.1168T>C
ENST00000674628.2:c.1168T>C
ENST00000675540.2:c.1168T>C
ENST00000696733.1:c.1168T>C
ENST00000696734.1:c.1168T>C
ENST00000696736.1:c.1168T>C
ENST00000696737.1:c.1168T>C
ENST00000696921.1:n.2274T>C
ENST00000696922.1:n.1577T>C
ENST00000696923.1:c.1168T>C
ENST00000696924.1:c.1168T>C
ENST00000696925.1:n.1577T>C
ENST00000696927.1:n.771T>C
ENST00000696928.1:n.1365T>C
ENST00000343455.8:c.1168T>C
ENST00000393063.6:c.1168T>C
ENST00000526495.6:c.1168T>C
ENST00000532939.3:c.1168T>C
ENST00000556045.6:c.1168T>C
ENST00000674628.1:c.1168T>C
ENST00000675995.1:c.1168T>C
ENST00000343455.7:c.1168T>C
ENST00000393063.5:c.1168T>C
ENST00000526495.5:c.1168T>C
ENST00000527414.5:c.1168T>C
ENST00000541352.5:c.1168T>C
NM_001195573.1:c.1168T>C
NM_001271282.2:c.1168T>C
NM_001291628.1:c.1168T>C
NM_030621.4:c.1168T>C
NM_177438.2:c.1168T>C
NM_001271282.3:c.1168T>C
NM_001291628.2:c.1168T>C
NM_001395677.1:c.1168T>C
NM_001395678.1:c.1168T>C
NM_001395679.1:c.1168T>C
NM_001395680.1:c.1168T>C
NM_001395682.1:c.1168T>C
NM_001395683.1:c.1168T>C
NM_001395684.1:c.1168T>C
NM_001395685.1:c.1168T>C
NM_001395686.1:c.886T>C
NM_001395687.1:c.763T>C
NM_001395688.1:c.763T>C
NM_001395689.1:c.763T>C
NM_001395690.1:c.763T>C
NM_001395691.1:c.601T>C
NM_001395692.1:c.1168T>C
NM_001395693.1:c.1168T>C
NM_001395694.1:c.1168T>C
NM_001395695.1:c.1168T>C
NM_001395696.1:c.763T>C
NM_001395697.1:c.-401T>C
NM_001395698.1:c.763T>C
NM_001395699.1:c.1168T>C
NM_001395700.1:c.1168T>C
NR_172715.1:n.1382T>C
NR_172716.1:n.1513T>C
NR_172717.1:n.1680T>C
NR_172718.1:n.1680T>C
NR_172719.1:n.1513T>C
NR_172720.1:n.1513T>C
More

Likely Benign

Met criteria codes 2
BP2 BP4
Not Met criteria codes 14
BS2 BS4 BS1 BA1 PS2 PS4 PS1 PP4 PP1 PP3 PM1 PM5 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.1168T>C variant in DICER1 is a missense variant predicted to cause substitution of tyrosine by histidine at amino acid 390 (p.Tyr390His). The total allele frequency in gnomAD v4.1.0 is 0.000002478 (4/1614020 alleles) with a highest population minor allele frequency of 0.000003390 (4/1180016 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). This variant has been observed in trans with the variant c.5479del, p.Leu1827fs (Internal lab contributors: International PPB Registry, Invitae, Prevention Genetics (all same case)) which is classified as pathogenic by the ClinGen DICER1 VCEP (SCV002540823.1) in an individual with Type II PPB and SLCT. The phase of the variants was confirmed by family testing (BP2). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.16); 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: BP2, BP4. (Bayesian Points: -2; VCEP specifications version 1.3.0; 08/27/2024)
Met criteria codes
BP2
This variant has been observed in trans with the variant c.5479del, p.Leu1827fs (Internal lab contributors: International PPB Registry, Invitae, Prevention Genetics (all same case)) which is classified as pathogenic by the ClinGen DICER1 VCEP (SCV002540823.1) in an individual with Type II PPB and SLCT. The phase of the variants was confirmed by family testing (BP2).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.16); MaxEntScan and SpliceAI: no effect on splicing) (BP4).
Not Met criteria codes
BS2
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
BA1
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
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
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
Another missense variant [c.1168T>C, p.Tyr390His] in the same codon has been reported (ClinVar Variation ID: 242033]. However, this variant has not yet met the criteria to be classified as pathogenic by the ClinGen DICER1 VCEP (PM5 not met).
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 0.000002478 (4/1614020 alleles) with a highest population minor allele frequency of 0.000003390 (4/1180016 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
Curation History
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