Submissions for variant NM_181458.4(PAX3):c.126C>A (p.Gly42=)

gnomAD frequency: 0.00026  dbSNP: rs369680052

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000272596	SCV000427912	benign	Craniofacial-deafness-hand syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000327618	SCV000427913	benign	Waardenburg syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000615913	SCV000711475	benign	not specified	2017-12-14	criteria provided, single submitter	clinical testing	p.Gly42Gly in exon 2 of PAX3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 0.56% (158/27968) of South Asian chromosomes including 2 homozygotes by the Genome Aggregation Datab ase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs369680052).
Invitae	RCV000953449	SCV001100022	benign	not provided	2023-10-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000953449	SCV001847137	benign	not provided	2018-12-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000953449	SCV004151496	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	PAX3: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003922444	SCV004738166	likely benign	PAX3-related condition	2019-09-26	criteria provided, single submitter	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).