NM_058172.6(ANTXR2):c.1074del (p.Ala359fs) AND Hyaline fibromatosis syndrome

Clinical significance:Pathogenic (Last evaluated: Nov 14, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV001261562.3

Allele description [Variation Report for NM_058172.6(ANTXR2):c.1074del (p.Ala359fs)]

NM_058172.6(ANTXR2):c.1074del (p.Ala359fs)

Gene:
ANTXR2:ANTXR cell adhesion molecule 2 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
4q21.21
Genomic location:
Preferred name:
NM_058172.6(ANTXR2):c.1074del (p.Ala359fs)
HGVS:
  • NC_000004.12:g.79984831del
  • NG_015987.1:g.93493del
  • NM_001145794.1:c.1074del
  • NM_001145794.2:c.1074del
  • NM_001286780.2:c.843del
  • NM_001286781.2:c.843del
  • NM_058172.6:c.1074delMANE SELECT
  • NP_001139266.1:p.Ala359fs
  • NP_001139266.1:p.Ala359fs
  • NP_001273709.1:p.Ala282fs
  • NP_001273710.1:p.Ala282fs
  • NP_477520.2:p.Ala359fs
  • NC_000004.11:g.80905985del
  • NM_058172.5:c.1074delT
Protein change:
A282fs
Links:
dbSNP: rs312262693
NCBI 1000 Genomes Browser:
rs312262693
Molecular consequence:
  • NM_001145794.1:c.1074del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001145794.2:c.1074del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001286780.2:c.843del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001286781.2:c.843del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_058172.6:c.1074del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
5

Condition(s)

Name:
Hyaline fibromatosis syndrome (HFS)
Synonyms:
HYALINOSIS, SYSTEMIC; Hyalinosis, Inherited Systemic
Identifiers:
MONDO: MONDO:0009229; MedGen: C2745948; Orphanet: 2028; OMIM: 228600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001438828Pathology and Clinical Laboratory Medicine,King Fahad Medical Citycriteria provided, single submitter
Pathogenicgermlineclinical testing

Citation Link,

SCV001445921Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diegocriteria provided, single submitter
Pathogenic
(May 28, 2019)
germlineclinical testing

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

SCV001523657Baylor Geneticscriteria provided, single submitter
Pathogenic
(Nov 14, 2019)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
Arabgermlineyes5not providednot providednot providednot providedclinical 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 Pathology and Clinical Laboratory Medicine,King Fahad Medical City, SCV001438828.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Arab5not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided5not providednot providednot provided

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV001445921.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This frameshifting variant in exon 13 of 16 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has been previously reported as a compound heterozygous and as a homozygous change in patients with hyaline fibromatosis syndrome (PMID: 14508707, 21328543). It is found within a hotspot on exon 13 which contains several recurrent frameshift variants that together account for approximately 60% of all pathogenic alleles in ANTXR2 (PMID: 23554269). Functional studies using patient fibroblasts and HeLa cells demonstrated that this variant leads to very low levels of mRNA expression and proteasome-mediated degradation of the mistranslated protein (PMID: 23554269). It is present in the heterozygous state in the gnomAD population database at a frequency of .004% (11/270038) and thus is presumed to be rare. Based on the available evidence, the p.Ala359HisfsTer50 variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV001523657.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 24, 2021

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