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]
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Variant: NM_177438.3(DICER1):c.1907+3A>T

CA915946406

820285 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: adff113f-436f-4442-b696-f379b967eaf2
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.3:c.1907+3A>T
NM_177438.3(DICER1):c.1907+3A>T
NC_000014.9:g.95115664T>A
CM000676.2:g.95115664T>A
NC_000014.8:g.95582001T>A
CM000676.1:g.95582001T>A
NC_000014.7:g.94651754T>A
NG_016311.1:g.46759A>T
ENST00000343455.8:c.1907+3A>T
ENST00000393063.6:c.1907+3A>T
ENST00000526495.6:c.1907+3A>T
ENST00000532939.3:c.1907+3A>T
ENST00000556045.6:c.1907+3A>T
ENST00000675995.1:c.*223+3A>T
ENST00000343455.7:c.1907+3A>T
ENST00000393063.5:c.1907+3A>T
ENST00000526495.5:c.1907+3A>T
ENST00000527414.5:c.1907+3A>T
ENST00000532458.1:n.496+3A>T
ENST00000541352.5:c.1907+3A>T
NM_001195573.1:c.1907+3A>T
NM_001271282.2:c.1907+3A>T
NM_001291628.1:c.1907+3A>T
NM_030621.4:c.1907+3A>T
NM_177438.2:c.1907+3A>T
NM_001271282.3:c.1907+3A>T
NM_001291628.2:c.1907+3A>T
NM_001395677.1:c.1907+3A>T
NM_001395678.1:c.1907+3A>T
NM_001395679.1:c.1907+3A>T
NM_001395680.1:c.1907+3A>T
NM_001395682.1:c.1907+3A>T
NM_001395683.1:c.1907+3A>T
NM_001395684.1:c.1907+3A>T
NM_001395685.1:c.1907+3A>T
NM_001395686.1:c.1625+3A>T
NM_001395687.1:c.1502+3A>T
NM_001395688.1:c.1502+3A>T
NM_001395689.1:c.1502+3A>T
NM_001395690.1:c.1502+3A>T
NM_001395691.1:c.1340+3A>T
NM_001395692.1:c.1907+3A>T
NM_001395693.1:c.1907+3A>T
NM_001395694.1:c.1907+3A>T
NM_001395695.1:c.1907+3A>T
NM_001395696.1:c.1502+3A>T
NM_001395697.1:c.224+3A>T
NM_001395698.1:c.1502+3A>T
NR_172715.1:n.2325+3A>T
NR_172716.1:n.2252+3A>T
NR_172717.1:n.2419+3A>T
NR_172718.1:n.2419+3A>T
NR_172719.1:n.2252+3A>T
NR_172720.1:n.2252+3A>T

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 2
BS3 PM2_Supporting
Not Met criteria codes 14
BA1 BS4 BS1 BP2 BP4 PS2 PS4 PS3 PS1 PP1 PP3 PM6 PM1 PM5

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

PDF
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.1907+3A>T variant in DICER1 is an intronic variant located in exon 11. The results from 2 in silico splicing predictors [MaxEntScan, SpliceAI] do not agree, supporting neither a deleterious nor benign impact on splicing. The variant is absent from gnomAD v2.1.1 and v3.1.1 (non-cancer) (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in any individuals with DICER1 syndrome. Sequencing of RNA from 3 patients showed that this variant does not affect splicing, indicating that this variant is unlikely to impact protein function (BS3; Internal contributor GTR: 61756). In summary, this variant meets the criteria to be classified as LIKELY BENIGN for DICER1 syndrome. Although there are both pathogenic and benign types of evidence for this variant, the pathogenic evidence is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS3, PM2_Supporting. (Bayesian Points: -3; VCEP specifications version 1; 02/11/2022)
Met criteria codes
BS3
Sequencing of RNA from 3 patients showed that this variant does not affect splicing, indicating that this variant is unlikely to impact protein function (BS3; Internal contributor GTR: 61756). Provided on 10/26/2021 VCEP Call
PM2_Supporting
Absent from gnomAD v2.1.1 (non-cancer) and v3.1.1 (non-cancer)
Not Met criteria codes
BA1
Absent from gnomAD v2.1.1
BS4
To our knowledge, this variant has not been reported in the literature in any individuals with DICER1 syndrome.
BS1
Absent from gnomAD v2.1.1
BP2
To our knowledge, this variant has not been reported in the literature in any individuals with DICER1 syndrome.
BP4
The results from 2 in silico splicing predictors [MaxEntScan, SpliceAI] do not agree, supporting neither a deleterious nor benign impact on splicing.
PS2
To our knowledge, this variant has not been reported in the literature in any individuals with DICER1 syndrome.
PS4
To our knowledge, this variant has not been reported in the literature in any individuals with DICER1 syndrome.
PS3
To our knowledge, functional assays have not been reported for this variant.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
To our knowledge, this variant has not been reported in the literature in any individuals with DICER1 syndrome.
PP3
The results from 2 in silico splicing predictors [MaxEntScan, SpliceAI] do not agree, supporting neither a deleterious nor benign impact on splicing.
PM6
To our knowledge, this variant has not been reported in the literature in any individuals with DICER1 syndrome.
PM1
This variant does not reside within a region of DICER1 that is defined as a mutational hotspot or critical functional domain by the ClinGen DICER1 VCEP.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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