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NM_177438.3(DICER1):c.4616C>T (p.Thr1539Met) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 19, 2024
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:
RCV000494503.14

Allele description [Variation Report for NM_177438.3(DICER1):c.4616C>T (p.Thr1539Met)]

NM_177438.3(DICER1):c.4616C>T (p.Thr1539Met)

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.4616C>T (p.Thr1539Met)
HGVS:
  • NC_000014.9:g.95096304G>A
  • NG_016311.1:g.66119C>T
  • NM_001195573.1:c.4616C>T
  • NM_001271282.3:c.4616C>T
  • NM_001291628.2:c.4616C>T
  • NM_030621.4:c.4616C>T
  • NM_177438.3:c.4616C>TMANE SELECT
  • NP_001182502.1:p.Thr1539Met
  • NP_001258211.1:p.Thr1539Met
  • NP_001278557.1:p.Thr1539Met
  • NP_085124.2:p.Thr1539Met
  • NP_803187.1:p.Thr1539Met
  • NP_803187.1:p.Thr1539Met
  • LRG_492t1:c.4616C>T
  • LRG_492:g.66119C>T
  • LRG_492p1:p.Thr1539Met
  • NC_000014.8:g.95562641G>A
  • NM_177438.2:c.4616C>T
  • p.T1539M
Protein change:
T1539M
Links:
dbSNP: rs747901058
NCBI 1000 Genomes Browser:
rs747901058
Molecular consequence:
  • NM_001195573.1:c.4616C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271282.3:c.4616C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001291628.2:c.4616C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_030621.4:c.4616C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_177438.3:c.4616C>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000581549Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Uncertain significance
(Sep 19, 2024)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Hodgkin lymphoma as a novel presentation of familial DICER1 syndrome.

Kuhlen M, Hönscheid A, Schemme J, Merz H, Mauz-Körholz C, Borkhardt A, Troeger A.

Eur J Pediatr. 2016 Apr;175(4):593-7. doi: 10.1007/s00431-015-2660-z. Epub 2015 Nov 3.

PubMed [citation]
PMID:
26526666

Whole genome sequencing reveals DICER1 as a candidate predisposing gene in familial Hodgkin lymphoma.

Bandapalli OR, Paramasivam N, Giangiobbe S, Kumar A, Benisch W, Engert A, Witzens-Harig M, Schlesner M, Hemminki K, Försti A.

Int J Cancer. 2018 Oct 15;143(8):2076-2078. doi: 10.1002/ijc.31576. Epub 2018 Jul 26. No abstract available.

PubMed [citation]
PMID:
29708584

Details of each submission

From Ambry Genetics, SCV000581549.7

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

Description

The p.T1539M variant (also known as c.4616C>T), located in coding exon 22 of the DICER1 gene, results from a C to T substitution at nucleotide position 4616. The threonine at codon 1539 is replaced by methionine, an amino acid with similar properties. This alteration has been reported in four individuals from one family who were all affected with DICER1-related tumors; however, these individuals were also found to carry a truncating DICER1 mutation in addition to this alteration (Kuhlen M et al. Eur. J. Pediatr. 2016 Apr;175:593-7). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Jan 13, 2025