U.S. flag

An official website of the United States government

NM_177438.3(DICER1):c.2614G>A (p.Ala872Thr) AND DICER1-related tumor predisposition

Germline classification:
Benign (3 submissions)
Last evaluated:
May 18, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000226630.27

Allele description [Variation Report for NM_177438.3(DICER1):c.2614G>A (p.Ala872Thr)]

NM_177438.3(DICER1):c.2614G>A (p.Ala872Thr)

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.2614G>A (p.Ala872Thr)
Other names:
NM_177438.2(DICER1):c.2614G>A; p.Ala872Thr
HGVS:
  • NC_000014.9:g.95107916C>T
  • NG_016311.1:g.54507G>A
  • NM_001195573.1:c.2614G>A
  • NM_001271282.3:c.2614G>A
  • NM_001291628.2:c.2614G>A
  • NM_030621.4:c.2614G>A
  • NM_177438.3:c.2614G>AMANE SELECT
  • NP_001182502.1:p.Ala872Thr
  • NP_001258211.1:p.Ala872Thr
  • NP_001278557.1:p.Ala872Thr
  • NP_085124.2:p.Ala872Thr
  • NP_803187.1:p.Ala872Thr
  • NP_803187.1:p.Ala872Thr
  • LRG_492t1:c.2614G>A
  • LRG_492:g.54507G>A
  • LRG_492p1:p.Ala872Thr
  • NC_000014.8:g.95574253C>T
  • NM_030621.4:c.2614G>A
  • NM_177438.2:c.2614G>A
  • p.A872T
Protein change:
A872T
Links:
dbSNP: rs149242330
NCBI 1000 Genomes Browser:
rs149242330
Molecular consequence:
  • NM_001195573.1:c.2614G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271282.3:c.2614G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001291628.2:c.2614G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_030621.4:c.2614G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_177438.3:c.2614G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000291641Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Benign
(Feb 1, 2024) 		germlineclinical testing

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

SCV000389755Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)		Benign
(Jan 13, 2018) 		germlineclinical testing

Citation Link,

SCV002540822ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen DICER1 ACMG Specifications DICER1 v1)		Benign
(May 18, 2022) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Ten years of DICER1 mutations: Provenance, distribution, and associated phenotypes.

de Kock L, Wu MK, Foulkes WD.

Hum Mutat. 2019 Nov;40(11):1939-1953. doi: 10.1002/humu.23877. Epub 2019 Aug 17.

PubMed [citation]
PMID:
31342592

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000291641.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Laboratory Services, Illumina, SCV000389755.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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

From ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen, SCV002540822.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The NM_177438.2:c.2614G>A (p.Ala872Thr) variant in DICER1 has the highest population minor allele frequency in gnomAD v2.1.1 is 0.00119 in non-Finnish European population, which is higher than the ClinGen DICER1 VCEP threshold (>0.0003) for BS1, and therefore meets this criterion (BS1). This variant has been observed in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (Internal lab contributors: 61756, 500031) and has been observed in a homozygous state in 5 healthy individuals (Internal lab contributors: 26957, 500031)(BS2). In vitro cleavage assay in HEK293 cells showed that this variant produces both 5p and 3p microRNAs from a pre-miRNA, indicating that this variant is unlikely to impact protein function (PMID: 31342592)(BS3_Supporting). The computational predictor REVEL gives a score of 0.488, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS1, BS2, BS3_Supporting, BP4. (Bayesian Points: -10; VCEP specifications version 1; 02/11/2022).

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

Last Updated: Oct 13, 2024