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NM_177438.3(DICER1):c.5276A>G (p.Lys1759Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 20, 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:
RCV000563154.6

Allele description [Variation Report for NM_177438.3(DICER1):c.5276A>G (p.Lys1759Arg)]

NM_177438.3(DICER1):c.5276A>G (p.Lys1759Arg)

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.5276A>G (p.Lys1759Arg)
Other names:
NM_177438.2(DICER1):c.5276A>G; p.Lys1759Arg
HGVS:
  • NC_000014.9:g.95093976T>C
  • NG_016311.1:g.68447A>G
  • NM_001195573.1:c.5276A>G
  • NM_001271282.3:c.5276A>G
  • NM_001291628.2:c.5276A>G
  • NM_030621.4:c.5276A>G
  • NM_177438.3:c.5276A>GMANE SELECT
  • NP_001182502.1:p.Lys1759Arg
  • NP_001258211.1:p.Lys1759Arg
  • NP_001278557.1:p.Lys1759Arg
  • NP_085124.2:p.Lys1759Arg
  • NP_803187.1:p.Lys1759Arg
  • NP_803187.1:p.Lys1759Arg
  • LRG_492t1:c.5276A>G
  • LRG_492:g.68447A>G
  • LRG_492p1:p.Lys1759Arg
  • NC_000014.8:g.95560313T>C
  • NM_177438.2:c.5276A>G
Protein change:
K1759R
Links:
dbSNP: rs144259142
NCBI 1000 Genomes Browser:
rs144259142
Molecular consequence:
  • NM_001195573.1:c.5276A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271282.3:c.5276A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001291628.2:c.5276A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_030621.4:c.5276A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_177438.3:c.5276A>G - 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
SCV000661890Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jan 20, 2023) 		germlineclinical testing

PubMed (3)
[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

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]
PMID:
24728327
PMCID:
PMC3984285

Pathogenic Mutations in Cancer-Predisposing Genes: A Survey of 300 Patients with Whole-Genome Sequencing and Lifetime Electronic Health Records.

He KY, Zhao Y, McPherson EW, Li Q, Xia F, Weng C, Wang K, He MM.

PLoS One. 2016;11(12):e0167847. doi: 10.1371/journal.pone.0167847.

PubMed [citation]
PMID:
27930734
PMCID:
PMC5145192
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000661890.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.K1759R variant (also known as c.5276A>G), located in coding exon 23 of the DICER1 gene, results from an A to G substitution at nucleotide position 5276. The lysine at codon 1759 is replaced by arginine, an amino acid with highly similar properties. This alteration was observed in a cohort of 45 Lebanese patients with a reported family history of breast cancer (Jalkh N et al. BMC Med. Genomics. 2017 02;10:8). In a cohort of 300 deceased patients, who underwent whole genome sequencing for 60 autosomal dominant cancer predisposition genes, this variant was detected and classified as a variant of uncertain significance by the authors. However, the specific phenotype of the patient(s) with this alteration was not reported (He KY et al. PLoS ONE, 2016 Dec;11:e0167847). This variant was also identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS One, 2014 Apr;9:e94554). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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: May 7, 2024