Evidence Repository - Clinical Genome Resources

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

BP7 BP4

PS2 PS4 PS3 BA1 PP3 PP4 PP1 PM1 PM6 PM2 BS4 BS3 BS1 BP2

Evidence Links 0

Expert Panel

DICER1 and miRNA-Processing Gene VCEP

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)

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"*?)

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

BA1

In gnomAD at low frequency

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

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

Approved on: 2022-05-18

Published on: 2022-07-08

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