NM_006214.4(PHYH):c.734G>A (p.Arg245Gln) AND Vitamin D-dependent rickets type II with alopecia

Germline classification:: Benign (1 submission)
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001258288.2

Allele description [Variation Report for NM_006214.4(PHYH):c.734G>A (p.Arg245Gln)]

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

Gene:

PHYH:phytanoyl-CoA 2-hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p13

Genomic location:

Preferred name:

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

HGVS:

NC_000010.11:g.13283784C>T
NG_012862.1:g.21347G>A
NM_001037537.2:c.434G>A
NM_001323080.2:c.434G>A
NM_001323082.2:c.740G>A
NM_001323083.2:c.470G>A
NM_001323084.2:c.440G>A
NM_006214.4:c.734G>AMANE SELECT
NP_001032626.1:p.Arg145Gln
NP_001032626.1:p.Arg145Gln
NP_001310009.1:p.Arg145Gln
NP_001310011.1:p.Arg247Gln
NP_001310012.1:p.Arg157Gln
NP_001310013.1:p.Arg147Gln
NP_006205.1:p.Arg245Gln
NC_000010.10:g.13325784C>T
NM_001037537.1:c.434G>A
NM_006214.3:c.734G>A
O14832:p.Arg245Gln

Protein change:

R145Q

Links:

UniProtKB: O14832#VAR_017491; dbSNP: rs62619919

NCBI 1000 Genomes Browser:

rs62619919

Molecular consequence:

NM_001037537.2:c.434G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323080.2:c.434G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323082.2:c.740G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323083.2:c.470G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323084.2:c.440G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006214.4:c.734G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Vitamin D-dependent rickets type II with alopecia (VDDR2A)
Synonyms:: GENERALIZED RESISTANCE TO 1,25-DIHYDROXYVITAMIN D; HYPOCALCEMIC VITAMIN D-RESISTANT RICKETS; PDDR IIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010186; MedGen: C0342646; Orphanet: 93160; OMIM: 277440

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001435215	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	research	PubMed (2) [See all records that cite these PMIDs] 10767344, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001435215

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign

germline

research

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease.

Jansen GA, Hogenhout EM, Ferdinandusse S, Waterham HR, Ofman R, Jakobs C, Skjeldal OH, Wanders RJ.

Hum Mol Genet. 2000 May 1;9(8):1195-200.

PubMed [citation]

PMID:: 10767344

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001435215.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 20, 2024

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