Submissions for variant NM_000277.3(PAH):c.707-7A>T

gnomAD frequency: 0.02868  dbSNP: rs62508624

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000274526	SCV000852119	benign	Phenylketonuria	2018-08-10	reviewed by expert panel	curation	PAH-specific ACMG/AMP criteria applied: BA1: Highest MAF=0.10514 in 1000G. 35 homozygotes in ExAC; BP4: HSF: No significant splicing motif alteration detected. This mutation has probably no impact on splicing. CADD=1.163344. In summary this variant meets criteria to be classified as benign for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (BA1, BP4).
Eurofins Ntd Llc (ga)	RCV000153636	SCV000203185	benign	not specified	2014-02-25	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000089046	SCV000281274	likely benign	not provided	2015-02-02	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Illumina Laboratory Services, Illumina	RCV000274526	SCV000375568	likely benign	Phenylketonuria	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000274526	SCV000629207	benign	Phenylketonuria	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000089046	SCV000696459	benign	not provided	2017-05-14	criteria provided, single submitter	clinical testing	Variant summary: c.707-7A>T in PAH gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing pattern, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.008876 (1049/ 118182 chrs tested), predominantly in individuals of African descent (0.08901; 910/ 10224 chrs tested), including 33 homozygotes. The observed frequencies exceed the maximum expected allele frequency for a pathogenic variant of 0.0079 suggesting that it is a benign polymorphism. The variant of interest has been reported in PKU individuals without strong evidence for causality, but is cited as Benign by a reputable database/clinical laboratory. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000089046	SCV001470037	benign	not provided	2020-07-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000089046	SCV001881880	benign	not provided	2019-02-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 2666653, 27884173)
Fulgent Genetics, Fulgent Genetics	RCV000274526	SCV002797257	benign	Phenylketonuria	2022-04-21	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000089046	SCV005235497	benign	not provided		criteria provided, single submitter	not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000089046	SCV000119651	not provided	not provided		no assertion provided	not provided
Natera, Inc.	RCV000274526	SCV002088647	benign	Phenylketonuria	2019-11-14	no assertion criteria provided	clinical testing