Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001514715 | SCV001722627 | benign | Phenylketonuria | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001797055 | SCV002039095 | likely benign | not provided | 2021-06-17 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000078525 | SCV003922613 | benign | not specified | 2023-03-27 | criteria provided, single submitter | clinical testing | Variant summary: PAH c.510-20_510-18dupATT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. The variant allele was found at a frequency of 0.0011 in 281816 control chromosomes, predominantly at a frequency of 0.011 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in PAH causing Phenylalanine Hydroxylase Deficiency (Phenylketonuria) phenotype (0.0079), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.510-20_510-18dupATT in individuals affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria) and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Eurofins Ntd Llc |
RCV000078525 | SCV000110381 | benign | not specified | 2012-12-21 | no assertion criteria provided | clinical testing |