NM_177438.3(DICER1):c.1880_1883del (p.Ile627fs) AND DICER1-related tumor predisposition

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: May 18, 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:: RCV000240940.6

Allele description [Variation Report for NM_177438.3(DICER1):c.1880_1883del (p.Ile627fs)]

NM_177438.3(DICER1):c.1880_1883del (p.Ile627fs)

Gene:

DICER1:dicer 1, ribonuclease III [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q32.13

Genomic location:

Preferred name:

NM_177438.3(DICER1):c.1880_1883del (p.Ile627fs)

Other names:

NM_030621.4(DICER1):c.1880_1883del; p.Ile627fs

HGVS:

NC_000014.9:g.95115694_95115697del
NG_016311.1:g.46729_46732del
NM_001195573.1:c.1880_1883del
NM_001271282.3:c.1880_1883del
NM_001291628.2:c.1880_1883del
NM_030621.4:c.1880_1883del
NM_177438.3:c.1880_1883delMANE SELECT
NP_001182502.1:p.Ile627fs
NP_001258211.1:p.Ile627fs
NP_001278557.1:p.Ile627fs
NP_085124.2:p.Ile627fs
NP_803187.1:p.I627Tfs*22
NP_803187.1:p.Ile627fs
NP_803187.1:p.Ile627fs
LRG_492t1:c.1880_1883del
LRG_492:g.46729_46732del
LRG_492p1:p.Ile627fs
NC_000014.8:g.95582031_95582034del
NM_177438.2:c.1880_1883del
NM_177438.2:c.1880_1883delTCAA
p.I627TfsX22

Protein change:

I627fs

Links:

dbSNP: rs886037680

NCBI 1000 Genomes Browser:

rs886037680

Molecular consequence:

NM_001195573.1:c.1880_1883del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001271282.3:c.1880_1883del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001291628.2:c.1880_1883del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_030621.4:c.1880_1883del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_177438.3:c.1880_1883del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000195578	International Pleuropulmonary Blastoma Registry, Children's Hospitals and Clinics of Minnesota - PPB-DICER1 Genetic study See additional submitters Children's National Medical Center	criteria provided, single submitter (Hill et al. (Science. 2009))	Pathogenic (Nov 10, 2014)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19556464, 26925222
SCV001371888	Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 1, 2019)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 26925222, 25741868
SCV002540829	ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen DICER1 ACMG Specifications DICER1 v1)	Pathogenic (May 18, 2022)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000195578

International Pleuropulmonary Blastoma Registry, Children's Hospitals and Clinics of Minnesota - PPB-DICER1 Genetic study

See additional submitters

criteria provided, single submitter

(Hill et al. (Science. 2009))

Pathogenic
(Nov 10, 2014)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001371888

Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 1, 2019)

germline

curation

PubMed (2)
[See all records that cite these PMIDs]

SCV002540829

ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen DICER1 ACMG Specifications DICER1 v1)

Pathogenic
(May 18, 2022)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing, curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

DICER1 mutations in familial pleuropulmonary blastoma.

Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ.

Science. 2009 Aug 21;325(5943):965. doi: 10.1126/science.1174334. Epub 2009 Jun 25.

PubMed [citation]

PMID:: 19556464
PMCID:: PMC3098036

Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model.

Brenneman M, Field A, Yang J, Williams G, Doros L, Rossi C, Schultz KA, Rosenberg A, Ivanovich J, Turner J, Gordish-Dressman H, Stewart D, Yu W, Harris A, Schoettler P, Goodfellow P, Dehner L, Messinger Y, Hill DA.

Version 2. F1000Res. 2015 [revised 2018 Jan 1];4:214. doi: 10.12688/f1000research.6746.2.

PubMed [citation]

PMID:: 26925222
PMCID:: PMC4712775

See all PubMed Citations (3)

Details of each submission

From International Pleuropulmonary Blastoma Registry, Children's Hospitals and Clinics of Minnesota - PPB-DICER1 Genetic study, SCV000195578.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research, SCV001371888.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	curation	PubMed (2)

Description

ACMG criteria met: PVS1, PM2, PP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen, SCV002540829.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

NM_177438.2(DICER1):c.1880_1883del (p.Ile627fs) variant in DICER1 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 11/27 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant received a total of 1 phenotype point across 1 unrelated probands/families meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting; PMIDs 26925222, ClinVar SCVs: SCV000581520.4, SCV000571419.5). The variant has been reported to segregate with disease in multiple affected family members, with 3 meioses from 1 family (PP1; ClinVar SCVs: SCV000581520.4). This variant is absent from gnomAD v2.1.1 and v3.1.1 (non-cancer)(PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PVS1, PS4_Supporting, PP1, PM2_Supporting (Bayesian Points: 11; VCEP specifications version 1; 02/11/2022).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

ClinVar

Relating variation to medicine