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NM_177438.3(DICER1):c.5441C>T (p.Ser1814Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 5, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV002349985.2

Allele description [Variation Report for NM_177438.3(DICER1):c.5441C>T (p.Ser1814Leu)]

NM_177438.3(DICER1):c.5441C>T (p.Ser1814Leu)

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.5441C>T (p.Ser1814Leu)
Other names:
NM_030621.4(DICER1):c.5441C>T; p.Ser1814Leu
HGVS:
  • NC_000014.9:g.95091289G>A
  • NG_016311.1:g.71134C>T
  • NM_001195573.1:c.5365-180C>T
  • NM_001271282.3:c.5441C>T
  • NM_001291628.2:c.5441C>T
  • NM_030621.4:c.5441C>T
  • NM_177438.3:c.5441C>TMANE SELECT
  • NP_001258211.1:p.Ser1814Leu
  • NP_001278557.1:p.Ser1814Leu
  • NP_085124.2:p.Ser1814Leu
  • NP_803187.1:p.Ser1814Leu
  • NP_803187.1:p.Ser1814Leu
  • LRG_492t1:c.5441C>T
  • LRG_492:g.71134C>T
  • LRG_492p1:p.Ser1814Leu
  • NC_000014.8:g.95557626G>A
  • NM_177438.2:c.5441C>T
  • p.S1814L
Protein change:
S1814L
Links:
dbSNP: rs1060503625
NCBI 1000 Genomes Browser:
rs1060503625
Molecular consequence:
  • NM_001195573.1:c.5365-180C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001271282.3:c.5441C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001291628.2:c.5441C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_030621.4:c.5441C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_177438.3:c.5441C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002652996Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 5, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Functional characterization of multiple DICER1 mutations in an adolescent.

Wu MK, de Kock L, Conwell LS, Stewart CJ, King BR, Choong CS, Hussain K, Sabbaghian N, MacRae IJ, Fabian MR, Foulkes WD.

Endocr Relat Cancer. 2016 Feb;23(2):L1-5. doi: 10.1530/ERC-15-0460. Epub 2015 Nov 6. No abstract available.

PubMed [citation]
PMID:
26545620

DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association.

Rutter MM, Jha P, Schultz KA, Sheil A, Harris AK, Bauer AJ, Field AL, Geller J, Hill DA.

J Clin Endocrinol Metab. 2016 Jan;101(1):1-5. doi: 10.1210/jc.2015-2169. Epub 2015 Nov 10.

PubMed [citation]
PMID:
26555935
PMCID:
PMC4701837

Details of each submission

From Ambry Genetics, SCV002652996.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.S1814L pathogenic mutation (also known as c.5441C>T), located in coding exon 24 of the DICER1 gene, results from a C to T substitution at nucleotide position 5441. The serine at codon 1814 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been identified in multiple individuals diagnosed with DICER1-associated tumors (Ambry internal data; Rutter MM et al. J. Clin. Endocrinol. Metab., 2016 Jan;101:1-5; Wu MK et al. Endocr. Relat. Cancer, 2016 Feb;23:L1-5). In addition, this variant segregated with disease in a family affected with early-onset multinodular goiters, differentiated thyroid cancer, and other DICER1-associated tumors (Rutter MM et al. J. Clin. Endocrinol. Metab., 2016 Jan;101:1-5). This variant demonstrated reduced 5p and 3p miRNA generation as compared to normal DICER1 protein in an in vitro cleavage assay (Wu MK et al. Endocr. Relat. Cancer, 2016). This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). In addition, this amino acid position is highly conserved in available vertebrate species and is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Nov 24, 2024