Submissions for variant NM_002834.5(PTPN11):c.854-21C>T

gnomAD frequency: 0.05308  dbSNP: rs41279090

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000033512	SCV000058297	benign	not specified	2013-03-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000033512	SCV000309214	benign	not specified		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000033512	SCV000920097	benign	not specified	2017-11-28	criteria provided, single submitter	clinical testing	Variant summary: The PTPN11 c.854-21C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SRp40, SF2/ASF and SC35. However, these predictions have yet to be confirmed by functional studies. This variant was found in 15911/276874 control chromosomes (626 homozygotes) at a frequency of 0.0574666, which is approximately 900 times the estimated maximal expected allele frequency of a pathogenic PTPN11 variant (0.0000625), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000157028	SCV001159315	benign	Noonan syndrome	2018-09-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001711141	SCV001945675	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315537	SCV004017213	benign	Juvenile myelomonocytic leukemia	2023-07-07	criteria provided, single submitter	clinical testing