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_177438.2(DICER1):c.1408G>T (p.Glu470Ter)

CA10586458

254287 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 5c12ee63-fea6-450a-8b8b-d08cd2bf3f94
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.1408G>T
NM_177438.2(DICER1):c.1408G>T (p.Glu470Ter)
NC_000014.9:g.95117723C>A
CM000676.2:g.95117723C>A
NC_000014.8:g.95584060C>A
CM000676.1:g.95584060C>A
NC_000014.7:g.94653813C>A
NG_016311.1:g.44700G>T
ENST00000343455.8:c.1408G>T
ENST00000393063.6:c.1408G>T
ENST00000526495.6:c.1408G>T
ENST00000532939.3:c.1408G>T
ENST00000556045.6:c.1408G>T
ENST00000674628.1:c.1408G>T
ENST00000675995.1:c.1408G>T
ENST00000343455.7:c.1408G>T
ENST00000393063.5:c.1408G>T
ENST00000526495.5:c.1408G>T
ENST00000527414.5:c.1408G>T
ENST00000532458.1:n.112G>T
ENST00000541352.5:c.1408G>T
NM_001195573.1:c.1408G>T
NM_001271282.2:c.1408G>T
NM_001291628.1:c.1408G>T
NM_030621.4:c.1408G>T
NM_001271282.3:c.1408G>T
NM_001291628.2:c.1408G>T
NM_177438.3:c.1408G>T
NM_001395677.1:c.1408G>T
NM_001395678.1:c.1408G>T
NM_001395679.1:c.1408G>T
NM_001395680.1:c.1408G>T
NM_001395682.1:c.1408G>T
NM_001395683.1:c.1408G>T
NM_001395684.1:c.1408G>T
NM_001395685.1:c.1408G>T
NM_001395686.1:c.1126G>T
NM_001395687.1:c.1003G>T
NM_001395688.1:c.1003G>T
NM_001395689.1:c.1003G>T
NM_001395690.1:c.1003G>T
NM_001395691.1:c.841G>T
NM_001395692.1:c.1408G>T
NM_001395693.1:c.1408G>T
NM_001395694.1:c.1408G>T
NM_001395695.1:c.1408G>T
NM_001395696.1:c.1003G>T
NM_001395697.1:c.-161G>T
NM_001395698.1:c.1003G>T
NR_172715.1:n.1826G>T
NR_172716.1:n.1753G>T
NR_172717.1:n.1920G>T
NR_172718.1:n.1920G>T
NR_172719.1:n.1753G>T
NR_172720.1:n.1753G>T
NM_177438.3(DICER1):c.1408G>T (p.Glu470Ter)
More

Pathogenic

Met criteria codes 4
PVS1 PP4 PM2_Supporting PS4_Supporting
Not Met criteria codes 11
PS2 PS3 PS1 BA1 PP1 PM6 PM1 BS4 BS3 BS1 BP2

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.1408G>T (p.Glu470Ter) variant in DICER1 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 9/27 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant received a total of 1 phenotype points across 1 family meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; PMIDs 26925222, 28323992, 30178239, 30339877). At least one patient with this variant was found to have a somatic second hit in a recognized DICER1 hotspot codon on tumor sequencing, which is highly specific for DICER1 syndrome (PP4, PMID 28323992). This variant is absent from gnomAD v2.1.1 and v3.1.1 (non-cancer) (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: (PVS1, PS4_supporting, PP4, PM2_supporting. (Bayesian Points: 11; VCEP specifications version 1; 02/11/2022)
Met criteria codes
PVS1
Predicted to undergo NMD: Stop codon 5’ of p.Pro1850
PP4
Somatic c.5126A>G (p.Asp1709Gly) identified in individual with nodular hyperplasia (PMID: 28323992)
PM2_Supporting
Absent gnomAD v2.1.1 (non-cancer). Over 20x coverage in >90% individuals.
PS4_Supporting
Identified in a family with features of DICER1 syndrome (PMID: 26925222, 28323992, 30178239, 30339877, internal laboratory contributors).
Not Met criteria codes
PS2
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
PS1
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
PP1
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
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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