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.3428T>C (p.Leu1143Pro)

CA349475

220594 (ClinVar)

Gene: DICER1

Condition: dicer1 syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6cde00c2-e953-4b0e-8669-393eef83e7fd

Approved on: 2022-05-18

Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.3428T>C

NM_177438.2(DICER1):c.3428T>C (p.Leu1143Pro)

NC_000014.9:g.95103968A>G

CM000676.2:g.95103968A>G

NC_000014.8:g.95570305A>G

CM000676.1:g.95570305A>G

NC_000014.7:g.94640058A>G

NG_016311.1:g.58455T>C

ENST00000343455.8:c.3428T>C

ENST00000393063.6:c.3428T>C

ENST00000526495.6:c.3428T>C

ENST00000532939.3:c.3428T>C

ENST00000556045.6:c.3428T>C

ENST00000675540.1:n.1173T>C

ENST00000675995.1:c.*1744T>C

ENST00000343455.7:c.3428T>C

ENST00000393063.5:c.3428T>C

ENST00000526495.5:c.3428T>C

ENST00000527414.5:c.3428T>C

ENST00000541352.5:c.3428T>C

ENST00000554367.1:n.637T>C

ENST00000556045.5:c.122T>C

NM_001195573.1:c.3428T>C

NM_001271282.2:c.3428T>C

NM_001291628.1:c.3428T>C

NM_030621.4:c.3428T>C

NM_001271282.3:c.3428T>C

NM_001291628.2:c.3428T>C

NM_177438.3:c.3428T>C

NM_001395677.1:c.3428T>C

NM_001395678.1:c.3428T>C

NM_001395679.1:c.3428T>C

NM_001395680.1:c.3428T>C

NM_001395682.1:c.3428T>C

NM_001395683.1:c.3428T>C

NM_001395684.1:c.3428T>C

NM_001395685.1:c.3428T>C

NM_001395686.1:c.3146T>C

NM_001395687.1:c.3023T>C

NM_001395688.1:c.3023T>C

NM_001395689.1:c.3023T>C

NM_001395690.1:c.3023T>C

NM_001395691.1:c.2861T>C

NM_001395692.1:c.3428T>C

NM_001395693.1:c.3428T>C

NM_001395694.1:c.3428T>C

NM_001395695.1:c.3428T>C

NM_001395696.1:c.3023T>C

NM_001395697.1:c.1745T>C

NR_172715.1:n.3846T>C

NR_172716.1:n.4030T>C

NR_172717.1:n.3940T>C

NR_172718.1:n.3863T>C

NR_172719.1:n.3696T>C

NR_172720.1:n.3773T>C

NM_177438.3(DICER1):c.3428T>C (p.Leu1143Pro)

Benign

BS1 BS2 BP4

BS4 BS3 BP2 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PM6 PM2 PM1 PM5

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.3428T>C variant in DICER1 is a missense variant predicted to cause substitution of leucine by proline at amino acid 1143 (p.Leu1143Pro). This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2; GTRs: 500031, 61756). The highest population minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.0029 (69/23442 alleles; FAF=0.0020) in African/African-American population, which is higher than the ClinGen DICER1 VCEP threshold (>0.0003) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.102, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as BENIGN for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2, BS1, BP4. (Bayesian Points: -9; VCEP specifications version 1; 02/11/2022)

BS1

99/41130 African/AA = 0.0024 gnomAD 3.1 (non-cancer); 69/23442 African/AA= 0.0029 gnomAD 2.1.1 (non-cancer); no homozygotes

BS2

This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2; Invitae SCV000261260.8, Ambry SCV000661830.3)

BP4

Score = 0.102, REVEL score <0.5; no splicing impact predicted

BS4