NM_021926.4(ALX4):c.653G>A (p.Arg218Gln) AND Parietal foramina 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 8, 2012
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000005318.6

Allele description [Variation Report for NM_021926.4(ALX4):c.653G>A (p.Arg218Gln)]

NM_021926.4(ALX4):c.653G>A (p.Arg218Gln)

Gene:

ALX4:ALX homeobox 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_021926.4(ALX4):c.653G>A (p.Arg218Gln)

HGVS:

NC_000011.10:g.44275472C>T
NG_015809.1:g.39695G>A
NM_021926.4:c.653G>AMANE SELECT
NP_068745.2:p.Arg218Gln
LRG_1256t1:c.653G>A
LRG_1256:g.39695G>A
LRG_1256p1:p.Arg218Gln
NC_000011.9:g.44297022C>T
Q9H161:p.Arg218Gln

Protein change:

R218Q; ARG218GLN

Links:

UniProtKB: Q9H161#VAR_010785; OMIM: 605420.0003; dbSNP: rs104894193

NCBI 1000 Genomes Browser:

rs104894193

Molecular consequence:

NM_021926.4:c.653G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Parietal foramina 2 (PFM2)
Identifiers:: MONDO: MONDO:0012309; MedGen: C1865044; Orphanet: 60015; OMIM: 609597

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025496	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2006)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 11137991, 16319823
SCV000056259	GeneReviews	no assertion criteria provided	pathologic (Nov 8, 2012)	not provided	curation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025496

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2006)

germline

literature only

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

SCV000056259

GeneReviews

no assertion criteria provided

pathologic
(Nov 8, 2012)

not provided

curation

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	not provided	not provided	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects.

Mavrogiannis LA, Antonopoulou I, Baxová A, Kutílek S, Kim CA, Sugayama SM, Salamanca A, Wall SA, Morriss-Kay GM, Wilkie AO.

Nat Genet. 2001 Jan;27(1):17-8.

PubMed [citation]

PMID:: 11137991

Enlarged parietal foramina caused by mutations in the homeobox genes ALX4 and MSX2: from genotype to phenotype.

Mavrogiannis LA, Taylor IB, Davies SJ, Ramos FJ, Olivares JL, Wilkie AO.

Eur J Hum Genet. 2006 Feb;14(2):151-8.

PubMed [citation]

PMID:: 16319823
PMCID:: PMC1477589

Details of each submission

From OMIM, SCV000025496.3

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

Description

In affected members of 2 unrelated families with parietal foramina-2 (PFM2; 609597), Mavrogiannis et al. (2001) identified a heterozygous c.653G-A transition in the ALX4 gene, resulting in an arg218-to-gln (R218Q) substitution. The mutation substituted a highly conserved residue in the N-terminal arm of the homeodomain that contacts the minor groove of DNA. In mouse, the identical mutation underlies the Strong luxoid allele, Alx4(lst), and abolishes DNA binding and transcriptional activation in vitro, with no detectable dominant-negative effect.

In a review of 7 patients from 2 unrelated families with parietal foramina due to the R218Q mutation, Mavrogiannis et al. (2006) found that the patients had disproportionately wide defects compared to patients with other mutations. The authors postulated a dominant-negative effect.

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

From GeneReviews, SCV000056259.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

Converted during submission to Pathogenic.

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

Last Updated: Apr 23, 2022

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