NM_000444.6(PHEX):c.208_212del (p.Val70fs) AND Familial X-linked hypophosphatemic vitamin D refractory rickets

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 12, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001271108.4

Allele description [Variation Report for NM_000444.6(PHEX):c.208_212del (p.Val70fs)]

NM_000444.6(PHEX):c.208_212del (p.Val70fs)

Gene:

PHEX:phosphate regulating endopeptidase X-linked [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

Xp22.11

Genomic location:

Preferred name:

NM_000444.6(PHEX):c.208_212del (p.Val70fs)

HGVS:

NC_000023.11:g.22047065GTAAA[1]
NG_007563.2:g.19263GTAAA[1]
NM_000444.6:c.208_212delMANE SELECT
NM_001282754.2:c.208_212del
NP_000435.3:p.Val70fs
NP_001269683.1:p.Val70fs
NC_000023.10:g.22065181_22065185del
NC_000023.10:g.22065183GTAAA[1]
NM_000444.5:c.208_212del
NM_000444.6:c.208_212delGTAAAMANE SELECT

Protein change:

V70fs

Links:

dbSNP: rs1927568587

NCBI 1000 Genomes Browser:

rs1927568587

Molecular consequence:

NM_000444.6:c.208_212del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282754.2:c.208_212del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Familial X-linked hypophosphatemic vitamin D refractory rickets (XLHRD)
Synonyms:: HYPOPHOSPHATEMIC VITAMIN D-RESISTANT RICKETS; Hypophosphatemic Rickets, X-Linked Dominant; Hypophosphatemia, vitamin D-resistant rickets; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010619; MedGen: C0733682; Orphanet: 89936; OMIM: 307800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001451952	MNM Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 25, 2019)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002787182	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 4, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004231760	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 12, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001451952

MNM Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 25, 2019)

de novo

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002787182

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 4, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004231760

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 12, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 MNM Diagnostics, SCV001451952.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This is a frame-shift mutation resulting in truncated protein, whose LOF is a known mechanism of X-linked hypophosphatemic rickets (XLHR) (PVS1). This is a de novo variant in a male patient with the disease and no family history (maternity confirmed) (PS2). It is located within functional protein domain (PM1), and patient's phenotype is specific for the disease of monogenic etiology (PP4).

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

From Fulgent Genetics, Fulgent Genetics, SCV002787182.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004231760.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

Last Updated: Nov 3, 2024

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