Submissions for variant NM_006206.6(PDGFRA):c.1364+6G>T

gnomAD frequency: 0.00004  dbSNP: rs368934617

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001038477	SCV001201947	uncertain significance	Gastrointestinal stromal tumor	2025-01-21	criteria provided, single submitter	clinical testing	This sequence change falls in intron 9 of the PDGFRA gene. It does not directly change the encoded amino acid sequence of the PDGFRA protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368934617, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. ClinVar contains an entry for this variant (Variation ID: 837196). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV005055147	SCV005689203	uncertain significance	Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal	2024-12-28	criteria provided, single submitter	clinical testing	The PDGFRA c.1364+6G>T intronic change results in a G to T substitution at the +6 position of intron 9 of the PDGFRA gene. Algorithms that predict the impact of sequence changes on splicing indicate that this change may impact splicing but to our knowledge these predictions have not been confirmed by RNA studies. This variant has a maximum subpopulation frequency of 0.01% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). To our knowledge, this variant has not been reported in individuals with PDGFRA-related conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004746204	SCV005358592	likely benign	PDGFRA-related disorder	2024-03-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).