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NM_177438.3(DICER1):c.5441C>T (p.Ser1814Leu) AND DICER1-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 25, 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:
RCV003389645.4

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:
DICER1-related disorder
Synonyms:
DICER1-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000993768PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 25, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV000993768.2

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

Description

The DICER1 c.5441C>T variant is predicted to result in the amino acid substitution p.Ser1814Leu. This variant has been reported to segregate in a family with DICER1-syndrome (Rutter et al. 2016. PubMed ID: 26555935) and reported in an additional unrelated individual with DICER1-syndrome (Wu et al. 2016. PubMed ID: 26545620). It has been reported in an individual with a somatic second hit in a recognized DICER1 hotspot codon on tumor sequencing (Rutter et al. 2016. PubMed ID: 26555935). Functional studies suggest this variant may lead to exon skipping and impact pre-miR122 cleavage (Figure 2, Wu et al. 2016. PubMed ID: 26545620). This variant occurs in the RNase IIIb domain, which is a hotspot for missense variants associated with DICER1-related neoplasms (Heravi-Moussavi et al. 2012. PubMed ID: 22187960; Foulkes et al. 2014. PubMed ID: 25176334; Chen et al. 2018. PubMed ID: 31893257). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic by the ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/412119/). This variant is interpreted as pathogenic.

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

Last Updated: Nov 24, 2024