Submissions for variant NM_006214.4(PHYH):c.734G>A (p.Arg245Gln)

gnomAD frequency: 0.00690  dbSNP: rs62619919

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179914	SCV000232234	benign	not specified	2014-11-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000179914	SCV000311433	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000950185	SCV000521053	benign	not provided	2020-08-06	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 14974078, 10767344, 27229527, 27535533)
Counsyl	RCV000665931	SCV000790142	likely benign	Phytanic acid storage disease	2017-03-06	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000665931	SCV000845255	benign	Phytanic acid storage disease	2024-09-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000950185	SCV001096473	benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258288	SCV001435215	benign	Vitamin D-dependent rickets type II with alopecia		criteria provided, single submitter	research	The p.Arg245Gln variant in PHYH has been identified in cis with p.Asp177Gly and in 4 individuals with Refsum disease, including 2 homozygotes and 2 heterozygotes (PMID: 10767344), and has been identified in >2% of European (Finnish) chromosomes and 9 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Arg245Gln variant may not impact protein function (PMID: 10767344). However, these types of assays may not accurately represent biological function. In summary, this variant meets criteria to be classified as benign for autosomal recessive Refsum disease.
CeGaT Center for Human Genetics Tuebingen	RCV000950185	SCV004126470	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	PHYH: BP4, BS1
Molecular Genetics, Royal Melbourne Hospital	RCV000665931	SCV004812635	benign	Phytanic acid storage disease	2023-05-04	criteria provided, single submitter	clinical testing	South Asian population allele frequency is 1.166% (rs62619919, 389/30616 alleles, 6 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
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004816303	SCV005070191	uncertain significance	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
University of Washington Center for Mendelian Genomics, University of Washington	RCV000755125	SCV000882947	likely pathogenic	Nonsyndromic cleft lip palate	2016-03-27	flagged submission	research
Illumina Laboratory Services, Illumina	RCV000665931	SCV001264065	uncertain significance	Phytanic acid storage disease	2017-04-27	flagged submission	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.