Submissions for variant NM_006206.6(PDGFRA):c.2562+4C>T

gnomAD frequency: 0.00001  dbSNP: rs374253258

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000467107	SCV000546560	uncertain significance	Gastrointestinal stromal tumor	2025-01-30	criteria provided, single submitter	clinical testing	This sequence change falls in intron 18 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 (rs374253258, gnomAD 0.004%). 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: 407368). 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.
Ambry Genetics	RCV001015942	SCV001176837	likely benign	Hereditary cancer-predisposing syndrome	2024-03-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Sema4, Sema4	RCV001015942	SCV002538568	uncertain significance	Hereditary cancer-predisposing syndrome	2021-04-22	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003899915	SCV004710125	likely benign	PDGFRA-related disorder	2023-03-22	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).