NM_177438.3(DICER1):c.2987+1G>A AND DICER1-related tumor predisposition

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 1, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000654454.10

Allele description [Variation Report for NM_177438.3(DICER1):c.2987+1G>A]

NM_177438.3(DICER1):c.2987+1G>A

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.2987+1G>A

HGVS:

NC_000014.9:g.95106040C>T
NG_016311.1:g.56383G>A
NM_001195573.1:c.2987+1G>A
NM_001271282.3:c.2987+1G>A
NM_001291628.2:c.2987+1G>A
NM_001395677.1:c.2987+1G>A
NM_001395678.1:c.2987+1G>A
NM_001395679.1:c.2987+1G>A
NM_001395680.1:c.2987+1G>A
NM_001395682.1:c.2987+1G>A
NM_001395683.1:c.2987+1G>A
NM_001395684.1:c.2987+1G>A
NM_001395686.1:c.2705+1G>A
NM_001395687.1:c.2582+1G>A
NM_001395688.1:c.2582+1G>A
NM_001395689.1:c.2582+1G>A
NM_001395690.1:c.2582+1G>A
NM_001395691.1:c.2420+1G>A
NM_001395692.1:c.2987+1G>A
NM_001395693.1:c.2987+1G>A
NM_001395694.1:c.2987+1G>A
NM_001395695.1:c.2987+1G>A
NM_001395696.1:c.2582+1G>A
NM_001395697.1:c.1304+1G>A
NM_030621.4:c.2987+1G>A
NM_177438.3:c.2987+1G>AMANE SELECT
LRG_492t1:c.2987+1G>A
LRG_492:g.56383G>A
NC_000014.8:g.95572377C>T
NM_177438.2:c.2987+1G>A
NR_172716.1:n.3333G>A

Links:

dbSNP: rs1555370248

NCBI 1000 Genomes Browser:

rs1555370248

Molecular consequence:

NR_172716.1:n.3333G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001195573.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001271282.3:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001291628.2:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395677.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395678.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395679.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395680.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395682.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395683.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395684.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395686.1:c.2705+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395687.1:c.2582+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395688.1:c.2582+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395689.1:c.2582+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395690.1:c.2582+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395691.1:c.2420+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395692.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395693.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395694.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395695.1:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395696.1:c.2582+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001395697.1:c.1304+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_030621.4:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_177438.3:c.2987+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000776348	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 26, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 19556464, 21266384, 28492532
SCV001372153	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] 28624956, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000776348

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 26, 2017)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001372153

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]

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	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000776348.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DICER1 are known to be pathogenic (PMID: 19556464, 21266384). This variant has not been reported in the literature in individuals with DICER1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 18 of the DICER1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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

From Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research, SCV001372153.2

#	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

Last Updated: Nov 18, 2024

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