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_177438.2(DICER1):c.2651-4T>G

CA7331198

543697 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7570cbda-3b38-456f-a9d5-834902f1b32d

HGVS expressions

NM_177438.2:c.2651-4T>G
NM_177438.2(DICER1):c.2651-4T>G
NC_000014.9:g.95107765A>C
CM000676.2:g.95107765A>C
NC_000014.8:g.95574102A>C
CM000676.1:g.95574102A>C
NC_000014.7:g.94643855A>C
NG_016311.1:g.54658T>G
ENST00000343455.8:c.2651-4T>G
ENST00000393063.6:c.2651-4T>G
ENST00000526495.6:c.2651-4T>G
ENST00000532939.3:c.2651-4T>G
ENST00000556045.6:c.2651-4T>G
ENST00000675540.1:n.473-4T>G
ENST00000675995.1:c.*967-4T>G
ENST00000343455.7:c.2651-4T>G
ENST00000393063.5:c.2651-4T>G
ENST00000526495.5:c.2651-4T>G
ENST00000527414.5:c.2651-4T>G
ENST00000541352.5:c.2651-4T>G
ENST00000556681.1:n.9T>G
NM_001195573.1:c.2651-4T>G
NM_001271282.2:c.2651-4T>G
NM_001291628.1:c.2651-4T>G
NM_030621.4:c.2651-4T>G
NM_001271282.3:c.2651-4T>G
NM_001291628.2:c.2651-4T>G
NM_177438.3:c.2651-4T>G
NM_001395677.1:c.2651-4T>G
NM_001395678.1:c.2651-4T>G
NM_001395679.1:c.2651-4T>G
NM_001395680.1:c.2651-4T>G
NM_001395682.1:c.2651-4T>G
NM_001395683.1:c.2651-4T>G
NM_001395684.1:c.2651-4T>G
NM_001395685.1:c.2651-4T>G
NM_001395686.1:c.2369-4T>G
NM_001395687.1:c.2246-4T>G
NM_001395688.1:c.2246-4T>G
NM_001395689.1:c.2246-4T>G
NM_001395690.1:c.2246-4T>G
NM_001395691.1:c.2084-4T>G
NM_001395692.1:c.2651-4T>G
NM_001395693.1:c.2651-4T>G
NM_001395694.1:c.2651-4T>G
NM_001395695.1:c.2651-4T>G
NM_001395696.1:c.2246-4T>G
NM_001395697.1:c.968-4T>G
NR_172715.1:n.3069-4T>G
NR_172716.1:n.2996-4T>G
NR_172717.1:n.3163-4T>G
NR_172718.1:n.3163-4T>G
NR_172719.1:n.2996-4T>G
NR_172720.1:n.2996-4T>G
NM_177438.3(DICER1):c.2651-4T>G

Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 14
PP3 PP4 PP1 BA1 PM1 PM6 PM2 BS4 BS3 BS1 BP2 PS2 PS4 PS3

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.2651-4T>G variant in DICER1 is an intronic variant resulting from a T to G substitution 4 nucleotides upstream from coding exon 17. It is not predicted by MaxEntScan or SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved, as the variant is the reference nucleotide in more than 3 mammalian species in the UCSC Genome Browser Multiz Alignments track (BP4, BP7). 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, BP7. (Bayesian Points: -2; VCEP specifications version 1; 02/11/2022)
Met criteria codes
BP7
intronic variant resulting from a T to G substitution 4 nucleotides upstream from coding exon 17. It is not predicted by MaxEntScan or SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved, as the variant is the reference nucleotide in more than 3 mammalian species in the UCSC Genome Browser Multiz Alignments track (Variant is reference allele in mouse, rat, horse, pig, and microbat)
BP4
Concordance of SpliceAI and MES that there is no splicing effect (*do we need to show "concordance of MaxEntScan and SpliceAI predicting either an increase in canonical splice site score or a decrease of the canonical splice site score by no more than 10% AND no putative cryptic splice sites are created"*?)
Not Met criteria codes
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No cases reported in literature or internal data
PP1
No cases reported in literature or internal data
BA1
In gnomAD at low frequency
PM1
Intronic variant
PM6
No cases reported in literature or internal data
PM2
In gnomAD at low frequency
BS4
No cases reported in literature or internal data
BS3
No published studies with functional info
BS1
In gnomAD at low frequency
BP2
No cases reported in literature or internal data
PS2
No cases reported in literature or internal data
PS4
Not reported in any individuals with any phenotype consistent with DICER1 **Seen in 10 cases at Invitae in cases with no personal or family history of DICER1 (one case also segregating a RAD51C variant) Seen in 4 cases at Ambry in cases with no personal or family history of DICER1
PS3
No published studies with functional info
Approved on: 2022-05-18
Published on: 2022-07-08
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