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]
Link to SEPIO compliant JSON-LD document

Variant: NM_177438.3(DICER1):c.4412C>T (p.Pro1471Leu)

CA16614180

412179 (ClinVar)

Gene: DICER1
Condition: DICER1-related tumor predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d57452e2-ac20-43ee-8474-59594d2620cb
Approved on: 2024-01-09
Published on: 2024-01-17

HGVS expressions

NM_177438.3:c.4412C>T
NM_177438.3(DICER1):c.4412C>T (p.Pro1471Leu)
NC_000014.9:g.95096508G>A
CM000676.2:g.95096508G>A
NC_000014.8:g.95562845G>A
CM000676.1:g.95562845G>A
NC_000014.7:g.94632598G>A
NG_016311.1:g.65915C>T
ENST00000343455.8:c.4412C>T
ENST00000393063.6:c.4412C>T
ENST00000526495.6:c.4412C>T
ENST00000532939.3:c.4412C>T
ENST00000556045.6:c.4412C>T
ENST00000675540.1:c.2157C>T
ENST00000675995.1:c.*2728C>T
ENST00000343455.7:c.4412C>T
ENST00000393063.5:c.4412C>T
ENST00000526495.5:c.4412C>T
ENST00000527414.5:c.4412C>T
ENST00000532939.2:c.447C>T
ENST00000541352.5:c.4412C>T
ENST00000556045.5:c.1106C>T
NM_001195573.1:c.4412C>T
NM_001271282.2:c.4412C>T
NM_001291628.1:c.4412C>T
NM_030621.4:c.4412C>T
NM_177438.2:c.4412C>T
NM_001271282.3:c.4412C>T
NM_001291628.2:c.4412C>T
NM_001395677.1:c.4412C>T
NM_001395678.1:c.4412C>T
NM_001395679.1:c.4412C>T
NM_001395680.1:c.4412C>T
NM_001395682.1:c.4412C>T
NM_001395683.1:c.4412C>T
NM_001395684.1:c.4412C>T
NM_001395685.1:c.4412C>T
NM_001395686.1:c.4130C>T
NM_001395687.1:c.4007C>T
NM_001395688.1:c.4007C>T
NM_001395689.1:c.4007C>T
NM_001395690.1:c.4007C>T
NM_001395691.1:c.3845C>T
NM_001395692.1:c.4412C>T
NM_001395693.1:c.4412C>T
NM_001395694.1:c.4412C>T
NM_001395695.1:c.4412C>T
NM_001395696.1:c.4007C>T
NM_001395697.1:c.2729C>T
NR_172715.1:n.4830C>T
NR_172716.1:n.5014C>T
NR_172717.1:n.4924C>T
NR_172718.1:n.4847C>T
NR_172719.1:n.4680C>T
NR_172720.1:n.4757C>T

Likely Benign

Met criteria codes 2
BS2_Supporting BP4
Not Met criteria codes 14
PM6 PM2 PM1 PM4 PM5 BA1 BS3 BS1 BP7 BP5 BP3 PS1 PS3 PS2

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.4412C>T variant in DICER1 is a missense variant predicted to cause substitution of Proline by Leucine at amino acid 1471 (p.Pro1471Leu). 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/GTRs). The highest population minor allele frequency in gnomAD v3.1.2 is 0.00001543 (1/64,794 alleles) in the 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: 0.04 MaxEntScan and SpliceAI: no effect on splicing) (BP4). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4, BS2_Supporting. (Bayesian Points: -2; VCEP specifications version 1.2.0; 01/09/2024)
Met criteria codes
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/GTRs).
BP4
In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.04 MaxEntScan and SpliceAI: no effect on splicing) (BP4).
Not Met criteria codes
PM6
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 v3.1.2 is 0.00001543 (1/64,794 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
PM1
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
PM5
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
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
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
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
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
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