U.S. flag

An official website of the United States government

NM_177438.3(DICER1):c.4740G>T (p.Gln1580His) AND DICER1-related tumor predisposition

Germline classification:
Likely benign (2 submissions)
Last evaluated:
Oct 25, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000468344.14

Allele description [Variation Report for NM_177438.3(DICER1):c.4740G>T (p.Gln1580His)]

NM_177438.3(DICER1):c.4740G>T (p.Gln1580His)

Gene:
DICER1:dicer 1, ribonuclease III [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q32.13
Genomic location:
Preferred name:
NM_177438.3(DICER1):c.4740G>T (p.Gln1580His)
Other names:
NM_177438.3(DICER1):c.4740G>T; p.Gln1580His
HGVS:
  • NC_000014.9:g.95096180C>A
  • NG_016311.1:g.66243G>T
  • NM_001195573.1:c.4740G>T
  • NM_001271282.3:c.4740G>T
  • NM_001291628.2:c.4740G>T
  • NM_030621.4:c.4740G>T
  • NM_177438.3:c.4740G>TMANE SELECT
  • NP_001182502.1:p.Gln1580His
  • NP_001258211.1:p.Gln1580His
  • NP_001278557.1:p.Gln1580His
  • NP_085124.2:p.Gln1580His
  • NP_803187.1:p.Gln1580His
  • NP_803187.1:p.Gln1580His
  • LRG_492t1:c.4740G>T
  • LRG_492:g.66243G>T
  • LRG_492p1:p.Gln1580His
  • NC_000014.8:g.95562517C>A
  • NM_177438.2:c.4740G>T
  • p.Q1580H
Protein change:
Q1580H
Links:
dbSNP: rs369465519
NCBI 1000 Genomes Browser:
rs369465519
Molecular consequence:
  • NM_001195573.1:c.4740G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271282.3:c.4740G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001291628.2:c.4740G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_030621.4:c.4740G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_177438.3:c.4740G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
DICER1-related tumor predisposition
Synonyms:
DICER1-related pleuropulmonary blastoma cancer predisposition syndrome; DICER1 syndrome
Identifiers:
MONDO: MONDO:0100216; MedGen: C3839822

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000553622Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely benign
(Jan 15, 2024) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002599114ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen DICER1 VCEP v1.1.0)		Likely benign
(Oct 25, 2022) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000553622.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen, SCV002599114.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_177438.2:c.4740G>T variant in DICER1 is a missense variant predicted to cause substitution of glutamine by histidine at amino acid 1580 (p.Gln1580His). 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/GTRs: 500031, 61756). The highest population minor allele frequency in gnomAD (non-cancer) v2.1.1 is 0.00003 (3/102668 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). In vitro cleavage assay in HEK293 cells showed that this variant produces both 5p and 3p microRNAs from a pre-miRNA, indicating that this variant is unlikely to impact protein function (BS3_Supporting; Wu 2018, McGill University). The computational predictor REVEL gives a score of 0.696, which is neither above nor below the thresholds predicting a damaging or benign impact on DICER1 function. 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: BS2_Supporting, BS3_Supporting. (Bayesian Points: -2; VCEP specifications version 1.1.0; 10/25/2022)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024