ClinVar Miner

Submissions for variant NM_177438.2(DICER1):c.3553G>A (p.Ala1185Thr) (rs150514959)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000989255 SCV000291663 likely benign DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2020-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000573896 SCV000661803 likely benign Hereditary cancer-predisposing syndrome 2020-07-07 criteria provided, single submitter clinical testing In silico models in agreement (benign);No disease association in small case-control study
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000989255 SCV000891015 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2020-10-07 criteria provided, single submitter clinical testing The DICER1 c.3553G>A (p.Ala1185Thr) missense change has a maximum subpopulation frequency of 0.073% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/14-95570180-C-T). This is likely to be greater than the expected prevalence of a pathogenic variant in DICER1 (PMID: 24761742). This variant occurs in a gene where missense variants are more likely to be damaging based on methods described by Lek et al. (PP2; PMID: 27535533), and in silico tools do not agree on the effect of this variant on protein function. To our knowledge, this variant has not been reported in individuals with a personal or family history suggestive of DICER1 Tumor Predisposition syndrome (internal data and literature review). In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PP2.
Mendelics RCV000989255 SCV001139510 uncertain significance DICER1-related pleuropulmonary blastoma cancer predisposition syndrome 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287777 SCV001474506 uncertain significance none provided 2019-09-14 criteria provided, single submitter clinical testing The DICER1 c.3553G>A; p.Ala1185Thr variant (rs150514959), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 133970). This variant is found in the general population with an overall allele frequency of 0.02% (49/282800 alleles) in the Genome Aggregation Database. The alanine at codon 1185 is moderately conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time.
ITMI RCV000120639 SCV000084800 not provided not specified 2013-09-19 no assertion provided reference population

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