ClinVar Miner

Submissions for variant NM_006206.6(PDGFRA):c.1631T>C (p.Val544Ala)

gnomAD frequency: 0.00012  dbSNP: rs181854060
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232812 SCV000289165 likely benign Gastrointestinal stromal tumor 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001012503 SCV001172963 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-24 criteria provided, single submitter clinical testing The p.V544A variant (also known as c.1631T>C), located in coding exon 10 of the PDGFRA gene, results from a T to C substitution at nucleotide position 1631. The valine at codon 544 is replaced by alanine, an amino acid with similar properties. This variant has been identified in an individual with isolated cleft palate, a cohort of 681 ancestrally diverse, healthy subjects, and at least one patient with a personal and family history of breast and/or ovarian cancer (Rattanasopha S et al. Eur. J. Hum. Genet. 2012 Oct;20:1058-62; Bodian DL et al. PLoS ONE. 2014 Apr;9:e94554; Maxwell KN et al. Am. J. Hum. Genet. 2016 May;98:801-817). This amino acid position is not well 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.
Sema4, Sema4 RCV001012503 SCV002538552 likely benign Hereditary cancer-predisposing syndrome 2020-07-31 criteria provided, single submitter curation
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153316 SCV003843653 likely pathogenic Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003485526 SCV004235741 uncertain significance Idiopathic hypereosinophilic syndrome 2023-04-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003944861 SCV004762060 uncertain significance PDGFRA-related condition 2023-12-19 criteria provided, single submitter clinical testing The PDGFRA c.1631T>C variant is predicted to result in the amino acid substitution p.Val544Ala. This variant was reported in an individual with isolated cleft palate (Rattanasopha et al. 2012. PubMed ID: 22473090). This variant was also identified in a study of a healthy, ancestrally diverse cohort (Supplementary Table S1, Bodian et al. 2014. PubMed ID: 24728327) and was reported as a variant of uncertain significance in an analysis of variants identified in families affected by breast cancer (Supplementary Table S5, Maxwell et al. 2016. PubMed ID: 27153395). This variant is reported in 0.15% of alleles in individuals of East Asian descent in gnomAD, including two homozygote findings. This variant has conflicting interpretations of likely benign, uncertain significance in likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/39617/). Although we suspect that 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.
OMIM RCV000032818 SCV000056586 uncertain significance Isolated cleft palate 2012-10-01 no assertion criteria provided literature only
ITMI RCV000121781 SCV000085979 not provided not specified 2013-09-19 no assertion provided reference population

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