Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000478.6(ALPL):c.881A>C (p.Asp294Ala)

Help
Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Sep 15, 2021)
Last evaluated:
Apr 1, 2021
Accession:
VCV000013664.8
Variation ID:
13664
Description:
single nucleotide variant
Help

NM_000478.6(ALPL):c.881A>C (p.Asp294Ala)

Allele ID
28703
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p36.12
Genomic location
1: 21573683 (GRCh38) GRCh38 UCSC
1: 21900176 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P05186:p.Asp294Ala
NC_000001.10:g.21900176A>C
NC_000001.11:g.21573683A>C
... more HGVS
Protein change
D294A, D217A, D239A
Other names
D277A
Canonical SPDI
NC_000001.11:21573682:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00010
The Genome Aggregation Database (gnomAD), exomes 0.00004
The Genome Aggregation Database (gnomAD) 0.00010
Links
ClinGen: CA256921
UniProtKB: P05186#VAR_006163
OMIM: 171760.0003
dbSNP: rs121918002
Varsome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Apr 1, 2021 RCV000224505.5
Pathogenic 2 criteria provided, single submitter May 19, 2016 RCV000589324.2
Pathogenic 1 no assertion criteria provided Oct 15, 1992 RCV000014650.26
Pathogenic 1 no assertion criteria provided Oct 15, 1992 RCV000014651.28
Pathogenic 1 no assertion criteria provided Oct 15, 1992 RCV000014652.20
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ALPL - - GRCh38
GRCh37
531 547

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 20, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001215060.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces aspartic acid with alanine at codon 294 of the ALPL protein (p.Asp294Ala). The aspartic acid residue is moderately conserved and there … (more)
Pathogenic
(Apr 01, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001875252.1
Submitted: (Sep 15, 2021)
Evidence details
Comment:
Published in vitro functional studies of this variant (reported as D277A based on alternate nomenclature) indicate reduced alkaline phosphatase activityof the protein due to impaired … (more)
Pathogenic
(May 19, 2016)
criteria provided, single submitter
Method: clinical testing
Hypophosphatasia
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696804.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: The ALPL c.881A>C (p.Asp294Ala) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant … (more)
Pathogenic
(Nov 30, 2019)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Blueprint Genetics
Accession: SCV001832440.1
Submitted: (Sep 01, 2021)
Comment:
Patient analyzed with Comprehensive Skeletal Dysplasias and Disorders Panel
Evidence details
Pathogenic
(Dec 30, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000280986.2
Submitted: (Oct 05, 2017)
Evidence details
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Hypophosphatasia
Allele origin: germline
Natera, Inc.
Accession: SCV001459882.1
Submitted: (Dec 28, 2020)
Evidence details
Pathogenic
(Oct 15, 1992)
no assertion criteria provided
Method: literature only
HYPOPHOSPHATASIA, INFANTILE
Allele origin: germline
OMIM
Accession: SCV000034905.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Oct 15, 1992)
no assertion criteria provided
Method: literature only
HYPOPHOSPHATASIA, CHILDHOOD
Allele origin: germline
OMIM
Accession: SCV000034906.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Oct 15, 1992)
no assertion criteria provided
Method: literature only
HYPOPHOSPHATASIA, ADULT
Allele origin: germline
OMIM
Accession: SCV000034907.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)

Functional evidence

Help
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Help
Title Author Journal Year Link
Hypophosphatasia: validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients. Whyte MP Bone 2015 PMID: 25731960
Enzyme-replacement therapy in life-threatening hypophosphatasia. Whyte MP The New England journal of medicine 2012 PMID: 22397652
Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. Whyte MP Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2009 PMID: 19335222
Characterization of 11 novel mutations in the tissue non-specific alkaline phosphatase gene responsible for hypophosphatasia and genotype-phenotype correlations. Brun-Heath I Molecular genetics and metabolism 2005 PMID: 15694177
Possible interference between tissue-non-specific alkaline phosphatase with an Arg54-->Cys substitution and acounterpart with an Asp277-->Ala substitution found in a compound heterozygote associated with severe hypophosphatasia. Fukushi-Irié M The Biochemical journal 2000 PMID: 10839996
Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. Henthorn PS Proceedings of the National Academy of Sciences of the United States of America 1992 PMID: 1409720

Text-mined citations for rs121918002...

Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 18, 2021