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]

Variant: NM_177438.3(DICER1):c.4889G>T (p.Arg1630Leu)

CA390866465

933119 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 670b674a-e55d-4165-b5ac-c303f3833025
Approved on: 2024-01-09
Published on: 2024-01-17

HGVS expressions

NM_177438.3:c.4889G>T
NM_177438.3(DICER1):c.4889G>T (p.Arg1630Leu)
NC_000014.9:g.95096031C>A
CM000676.2:g.95096031C>A
NC_000014.8:g.95562368C>A
CM000676.1:g.95562368C>A
NC_000014.7:g.94632121C>A
NG_016311.1:g.66392G>T
ENST00000343455.8:c.4889G>T
ENST00000393063.6:c.4889G>T
ENST00000526495.6:c.4889G>T
ENST00000532939.3:c.4889G>T
ENST00000556045.6:c.4889G>T
ENST00000675540.1:c.2634G>T
ENST00000675995.1:c.*3205G>T
ENST00000343455.7:c.4889G>T
ENST00000393063.5:c.4889G>T
ENST00000526495.5:c.4889G>T
ENST00000527414.5:c.4889G>T
ENST00000532939.2:c.924G>T
ENST00000541352.5:c.4889G>T
ENST00000556045.5:c.1583G>T
NM_001195573.1:c.4889G>T
NM_001271282.2:c.4889G>T
NM_001291628.1:c.4889G>T
NM_030621.4:c.4889G>T
NM_177438.2:c.4889G>T
NM_001271282.3:c.4889G>T
NM_001291628.2:c.4889G>T
NM_001395677.1:c.4889G>T
NM_001395678.1:c.4889G>T
NM_001395679.1:c.4889G>T
NM_001395680.1:c.4889G>T
NM_001395682.1:c.4889G>T
NM_001395683.1:c.4889G>T
NM_001395684.1:c.4889G>T
NM_001395685.1:c.4889G>T
NM_001395686.1:c.4607G>T
NM_001395687.1:c.4484G>T
NM_001395688.1:c.4484G>T
NM_001395689.1:c.4484G>T
NM_001395690.1:c.4484G>T
NM_001395691.1:c.4322G>T
NM_001395692.1:c.4889G>T
NM_001395693.1:c.4889G>T
NM_001395694.1:c.4889G>T
NM_001395695.1:c.4889G>T
NM_001395696.1:c.4484G>T
NM_001395697.1:c.3206G>T
NR_172715.1:n.5307G>T
NR_172716.1:n.5491G>T
NR_172717.1:n.5401G>T
NR_172718.1:n.5324G>T
NR_172719.1:n.5157G>T
NR_172720.1:n.5234G>T
More

Uncertain Significance

Met criteria codes 2
BP4 PM2
Not Met criteria codes 24
BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP5 BP7 BA1 PVS1 PS1 PS2 PS4 PS3 PP4 PP1 PP3 PP2 PM5 PM3 PM1 PM4 PM6

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 1.2.0

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.4889G>T variant in DICER1 is a missense variant predicted to cause substitution of arginine by leucine at amino acid 1630 (p.Arg1630Leu). This variant is absent from gnomAD v2.1.1 and v3.1.2 (non-cancer) (PM2_Supporting). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.041; MaxEntScan and SpliceAI: no effect on splicing) (BP4). 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. (Bayesian Points: 0; VCEP specifications version 1.2.0; 01/09/2024)
Met criteria codes
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.041; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
PM2
This variant is absent from gnomAD v2.1.1 and v3.1.2 (non-cancer) (PM2_Supporting).
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
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
This evidence code is not currently applicable for DICER1 VCEP curations.
BP1
This evidence code is not currently applicable for DICER1 VCEP curations.
BP5
This evidence code is not currently applicable for DICER1 VCEP curations.
BP7
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
PVS1
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
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 in a single proband. (PS4 not met; GTR ID: 61756).
PS3
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
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.041; MaxEntScan and SpliceAI: no effect on splicing) (BP4).
PP2
This evidence code is not currently applicable for DICER1 VCEP curations.
PM5
Two different missense variants, c.4889G>A (p.Arg1630His) and c.4888C>T (p.Arg1630Cys), in the same codon have been reported (ClinVar Variation ID: 477226, 412061). The c.4889G>A (p.Arg1630His) has been classified as Likely Benign by two submitters (ClinVar SCV: SCV000658313.6, SCV000669323.4) and Uncertain Significance by one submitter (ClinVar SCV: SCV002533031.1). The c.4888C>T (p.Arg1630Cys) has been classified as Likely Benign by two submitters (ClinVar SCV: SCV001372189.2, SCV000553516.9) and Uncertain Significance by three submitters (ClinVar SCV: SCV001737458.1, SCV002533030.1, SCV000661940.4) (PM5 not met).
PM3
This evidence code is not currently applicable for DICER1 VCEP curations.
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.