Submissions for variant NM_000277.3(PAH):c.60+62C>T

gnomAD frequency: 0.34408  dbSNP: rs1522296

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000709703	SCV001250539	benign	Phenylketonuria	2019-11-08	reviewed by expert panel	curation	The c.60+62C>T intronic variant in PAH has a MAF of 0.3441 in gnomAD with 2,014 homozygotes.In summary, this variant meets criteria to be classified as benign for PAH. PAH-specific ACMG/AMP criteria applied: BA1, BS2, BP7.
Pars Genome Lab	RCV000709703	SCV001750014	benign	Phenylketonuria	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001598678	SCV001827402	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
H3Africa Consortium	RCV001703234	SCV002014653	benign	not specified	2020-10-28	criteria provided, single submitter	research	While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.521, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error.
Molecular Genetics, Royal Melbourne Hospital	RCV000709703	SCV004812732	benign	Phenylketonuria	2023-05-04	criteria provided, single submitter	clinical testing	African/African American population allele frequency is 48.34% (rs1522296, 4299/8672 alleles, 1055 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1
Breakthrough Genomics, Breakthrough Genomics	RCV001598678	SCV005235510	benign	not provided		criteria provided, single submitter	not provided
Clinical Laboratory, Xuzhou Maternity and Child Health Care Hospital	RCV000709703	SCV000839874	likely pathogenic	Phenylketonuria	2018-06-26	no assertion criteria provided	case-control
Reproductive Health Research and Development, BGI Genomics	RCV000709703	SCV001142436	benign	Phenylketonuria	2020-01-06	no assertion criteria provided	curation	NG_008690.2(NM_000277.2):c.60+62C>T in the gene PAH has an allele frequency of 0.496 in African subpopulation in the gnomAD database. A total of 2014 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001703234	SCV001930245	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001703234	SCV001954627	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003980322	SCV004798874	benign	PAH-related disorder	2021-02-18	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).