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.2256+6T>A

CA658798256

543574 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 8a1b55b6-175f-4e22-84cc-87ce60c33672
Approved on: 2023-03-01
Published on: 2023-03-01

HGVS expressions

NM_177438.3:c.2256+6T>A
NM_177438.3(DICER1):c.2256+6T>A
NC_000014.9:g.95111311A>T
CM000676.2:g.95111311A>T
NC_000014.8:g.95577648A>T
CM000676.1:g.95577648A>T
NC_000014.7:g.94647401A>T
NG_016311.1:g.51112T>A
ENST00000343455.8:c.2256+6T>A
ENST00000393063.6:c.2256+6T>A
ENST00000526495.6:c.2256+6T>A
ENST00000532939.3:c.2256+6T>A
ENST00000556045.6:c.2256+6T>A
ENST00000675540.1:n.78+6T>A
ENST00000675995.1:c.*572+6T>A
ENST00000343455.7:c.2256+6T>A
ENST00000393063.5:c.2256+6T>A
ENST00000526495.5:c.2256+6T>A
ENST00000527414.5:c.2256+6T>A
ENST00000541352.5:c.2256+6T>A
NM_001195573.1:c.2256+6T>A
NM_001271282.2:c.2256+6T>A
NM_001291628.1:c.2256+6T>A
NM_030621.4:c.2256+6T>A
NM_177438.2:c.2256+6T>A
NM_001271282.3:c.2256+6T>A
NM_001291628.2:c.2256+6T>A
NM_001395677.1:c.2256+6T>A
NM_001395678.1:c.2256+6T>A
NM_001395679.1:c.2256+6T>A
NM_001395680.1:c.2256+6T>A
NM_001395682.1:c.2256+6T>A
NM_001395683.1:c.2256+6T>A
NM_001395684.1:c.2256+6T>A
NM_001395685.1:c.2256+6T>A
NM_001395686.1:c.1974+6T>A
NM_001395687.1:c.1851+6T>A
NM_001395688.1:c.1851+6T>A
NM_001395689.1:c.1851+6T>A
NM_001395690.1:c.1851+6T>A
NM_001395691.1:c.1689+6T>A
NM_001395692.1:c.2256+6T>A
NM_001395693.1:c.2256+6T>A
NM_001395694.1:c.2256+6T>A
NM_001395695.1:c.2256+6T>A
NM_001395696.1:c.1851+6T>A
NM_001395697.1:c.573+6T>A
NM_001395698.1:c.1857T>A
NR_172715.1:n.2674+6T>A
NR_172716.1:n.2601+6T>A
NR_172717.1:n.2768+6T>A
NR_172718.1:n.2768+6T>A
NR_172719.1:n.2601+6T>A
NR_172720.1:n.2601+6T>A
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Uncertain Significance

Met criteria codes 4
PM2_Supporting PP1 PP3 PS4_Supporting
Not Met criteria codes 16
PS2 PS1 PS3 BA1 PP4 PM5 PM4 PM1 BS4 BS3 BS1 BS2 BP7 BP2 BP4 PVS1

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 1.1.0

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.2256+6T>A variant in DICER1 is an intronic variant which located in intron 14. This variant received a total of 1 phenotype points across 1 unrelated proband meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; Invitae, Ambry). The variant has been reported to segregate with DICER1 syndrome in 4 affected meioses from 1 family (PP1; Invitae, Ambry, NCI). This variant is absent from gnomAD v2.1.1 and v3.1.2 (non-cancer) (PM2_Supporting). The splice site predictors MaxEntScan and SpliceAI indicate that the variant impacts splicing, evidence that correlates with impact to DICER1 function (PP3). In summary, this variant meets the criteria to be classified as Uncertain Significance for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PS4_Supporting, PP1, PM2_Supporting, PP3. (Bayesian Points: 4; VCEP specifications version 1.1.0; 2/28/2023)
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v3.1.2 (non-cancer) (PM2_Supporting).
PP1
The variant has been reported to segregate with DICER1 syndrome in 4 affected meioses from 1 family (PP1_Supporting; Invitae, Ambry, NCI).
PP3
The splice site predictors MaxEntScan and SpliceAI indicate that the variant impacts splicing, evidence that correlates with impact to DICER1 function (PP3).
PS4_Supporting
This variant received a total of 1 phenotype points across 1 unrelated proband meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Moderate; Invitae, Ambry, NCI).
Not Met criteria codes
PS2
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
BA1
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
PM5
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
PM1
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
BS2
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
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
Curation History
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