NM_000444.6(PHEX):c.2045_2048dup (p.Phe684fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 23, 2022
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:: RCV003685667.1

Allele description [Variation Report for NM_000444.6(PHEX):c.2045_2048dup (p.Phe684fs)]

NM_000444.6(PHEX):c.2045_2048dup (p.Phe684fs)

Genes:

PTCHD1-AS:PTCHD1 antisense RNA (head to head) [Gene - HGNC]
PHEX:phosphate regulating endopeptidase X-linked [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

Xp22.11

Genomic location:

Preferred name:

NM_000444.6(PHEX):c.2045_2048dup (p.Phe684fs)

HGVS:

NC_000023.11:g.22227586_22227589dup
NG_007563.2:g.199783_199786dup
NG_007563.3:g.200263_200266dup
NM_000444.6:c.2045_2048dupMANE SELECT
NM_001282754.2:c.2045_2048dup
NP_000435.3:p.Phe684fs
NP_001269683.1:p.Phe684fs
NC_000023.10:g.22245702_22245703insAGCT
NC_000023.10:g.22245703_22245706dup
NR_073010.2:n.929_932dup

Protein change:

F684fs

Molecular consequence:

NM_000444.6:c.2045_2048dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282754.2:c.2045_2048dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_073010.2:n.929_932dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004408364	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 23, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9199930, 9768674, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004408364

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 23, 2022)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genomic organization of the human PEX gene mutated in X-linked dominant hypophosphatemic rickets.

Francis F, Strom TM, Hennig S, Böddrich A, Lorenz B, Brandau O, Mohnike KL, Cagnoli M, Steffens C, Klages S, Borzym K, Pohl T, Oudet C, Econs MJ, Rowe PS, Reinhardt R, Meitinger T, Lehrach H.

Genome Res. 1997 Jun;7(6):573-85. No abstract available.

PubMed [citation]

PMID:: 9199930

Mutational analysis of PHEX gene in X-linked hypophosphatemia.

Dixon PH, Christie PT, Wooding C, Trump D, Grieff M, Holm I, Gertner JM, Schmidtke J, Shah B, Shaw N, Smith C, Tau C, Schlessinger D, Whyte MP, Thakker RV.

J Clin Endocrinol Metab. 1998 Oct;83(10):3615-23.

PubMed [citation]

PMID:: 9768674

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004408364.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PHEX protein in which other variant(s) (p.Arg747*) have been determined to be pathogenic (PMID: 9199930, 9768674). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with hypophosphatemic rickets (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe684Alafs*34) in the PHEX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acid(s) of the PHEX protein.

#	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: Feb 28, 2024

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