ClinVar Miner

Submissions for variant NM_020975.6(RET):c.304G>A (p.Asp102Asn)

gnomAD frequency: 0.00002  dbSNP: rs201244749
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000554385 SCV000658467 uncertain significance Multiple endocrine neoplasia, type 2 2025-01-11 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 102 of the RET protein (p.Asp102Asn). This variant is present in population databases (rs201244749, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 135183). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Probably Damaging". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000567241 SCV000674850 benign Hereditary cancer-predisposing syndrome 2023-02-02 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV004528836 SCV000807043 uncertain significance RET-related disorder 2023-04-20 criteria provided, single submitter clinical testing The RET c.304G>A variant is predicted to result in the amino acid substitution p.Asp102Asn. This variant has been reported in individuals from a healthy, ancestrally diverse genome sequencing cohort (Table S1, Bodian et al. 2014. PubMed ID: 24728327). In silico tools predict this variant to be tolerated (Table S1, George Priya Doss et al. 2014. PubMed ID: 24336963; Table 1, Heineman et al . 2015. PubMed ID: 25733075). This variant is reported in 0.017% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-43596137-G-A) and has conflicting interpretations of benign and uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/135183/). Although we suspect this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Fulgent Genetics, Fulgent Genetics RCV002483229 SCV002777708 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2022-02-12 criteria provided, single submitter clinical testing
ITMI RCV000121987 SCV000086198 not provided not specified 2013-09-19 no assertion provided reference population

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.