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]

Variant: NM_177438.3(DICER1):c.1430A>G (p.Asn477Ser)

Curation Version - 1.0
Curation History
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CA16614267

412125 (ClinVar)

Gene: DICER1

Condition: DICER1-related tumor predisposition

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6f13e3ae-8929-466b-8faf-9639e96230a4

Approved on: 2024-10-22

Published on: 2024-11-13

HGVS expressions

NM_177438.3:c.1430A>G

NM_177438.3(DICER1):c.1430A>G (p.Asn477Ser)

NC_000014.9:g.95117701T>C

CM000676.2:g.95117701T>C

NC_000014.8:g.95584038T>C

CM000676.1:g.95584038T>C

NC_000014.7:g.94653791T>C

NG_016311.1:g.44722A>G

ENST00000529720.2:c.1430A>G

ENST00000531162.7:c.1430A>G

ENST00000674628.2:c.1430A>G

ENST00000675540.2:c.1430A>G

ENST00000696733.1:c.1430A>G

ENST00000696734.1:c.1430A>G

ENST00000696736.1:c.1430A>G

ENST00000696737.1:c.1430A>G

ENST00000696920.1:n.1693A>G

ENST00000696921.1:n.2536A>G

ENST00000696922.1:n.1839A>G

ENST00000696923.1:c.1430A>G

ENST00000696924.1:c.1430A>G

ENST00000696925.1:n.1839A>G

ENST00000696927.1:n.1033A>G

ENST00000696928.1:n.1627A>G

ENST00000343455.8:c.1430A>G

ENST00000393063.6:c.1430A>G

ENST00000526495.6:c.1430A>G

ENST00000532939.3:c.1430A>G

ENST00000556045.6:c.1430A>G

ENST00000674628.1:c.1430A>G

ENST00000675995.1:c.1430A>G

ENST00000343455.7:c.1430A>G

ENST00000393063.5:c.1430A>G

ENST00000526495.5:c.1430A>G

ENST00000527414.5:c.1430A>G

ENST00000532458.1:n.134A>G

ENST00000541352.5:c.1430A>G

NM_001195573.1:c.1430A>G

NM_001271282.2:c.1430A>G

NM_001291628.1:c.1430A>G

NM_030621.4:c.1430A>G

NM_177438.2:c.1430A>G

NM_001271282.3:c.1430A>G

NM_001291628.2:c.1430A>G

NM_001395677.1:c.1430A>G

NM_001395678.1:c.1430A>G

NM_001395679.1:c.1430A>G

NM_001395680.1:c.1430A>G

NM_001395682.1:c.1430A>G

NM_001395683.1:c.1430A>G

NM_001395684.1:c.1430A>G

NM_001395685.1:c.1430A>G

NM_001395686.1:c.1148A>G

NM_001395687.1:c.1025A>G

NM_001395688.1:c.1025A>G

NM_001395689.1:c.1025A>G

NM_001395690.1:c.1025A>G

NM_001395691.1:c.863A>G

NM_001395692.1:c.1430A>G

NM_001395693.1:c.1430A>G

NM_001395694.1:c.1430A>G

NM_001395695.1:c.1430A>G

NM_001395696.1:c.1025A>G

NM_001395697.1:c.-139A>G

NM_001395698.1:c.1025A>G

NR_172715.1:n.1848A>G

NR_172716.1:n.1775A>G

NR_172717.1:n.1942A>G

NR_172718.1:n.1942A>G

NR_172719.1:n.1775A>G

NR_172720.1:n.1775A>G

Likely Benign

BP4 BS2_Supporting

PS2 PS4 PM2 PM1 PM5 BA1 BS1

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 1.3.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

DICER1 and miRNA-Processing Gene VCEP

The NM_177438.3:c.1430A>G variant in DICER1 is a missense variant predicted to cause substitution of asparagine by serine at amino acid 477 (p.Asn477Ser). This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors). The total allele frequency in gnomAD v4.1.0 is 0.00001363 (22/1613880 alleles) with a highest population minor allele frequency of 0.00001667 (1/60000 alleles) in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met). This variant does not reside within a region of the RNAse IIIb domain that is defined as a mutational hotspot or critical functional domain by the ClinGen DICER1 VCEP (PM1 not met). In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.293; MaxEntScan and SpliceAI: no effect on splicing) (BP4). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS2_Supporting, BP4. (Bayesian Points: -2; VCEP specifications version 1.3.0; 10/22/2024)

BP4

In silico tools predict no damaging impact of the variant on protein function (REVEL: 0.293; MaxEntScan and SpliceAI: no effect on splicing) (BP4).

BS2_Supporting

This variant has been seen in 10 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2_Supporting; Internal lab contributors). There were 92 total cases without DICER1-related phenotypes observed across all these internal lab contributors.

PS2

This variant has been identified as a somatic variant in a sample from Wilm's tumor tissue in at least one individual (SCV001372137.2, PMID: 28825729; SCV005059472.1) (0 phenotype points).

PS4

This variant has been identified as a somatic variant in a sample from Wilm's tumor tissue in at least one individual (SCV001372137.2, PMID: 28825729; SCV005059472.1) (0 phenotype points).

PM2

The total allele frequency in gnomAD v4.1.0 is 0.00001363 (22/1613880 alleles) with a highest population minor allele frequency of 0.00001667 (1/60000 alleles) in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met).

PM1

This variant does not reside within a region of the RNAse IIIb domain that is defined as a mutational hotspot or critical functional domain by the ClinGen DICER1 VCEP (PM1 not met).

PM5

No other missense variants at the same amino acid position reported

BA1

BS1

Curation History

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