NM_014244.5(ADAMTS2):c.471C>G (p.Tyr157Ter) AND Ehlers-Danlos syndrome, dermatosparaxis type

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 28, 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:: RCV003030613.2

Allele description [Variation Report for NM_014244.5(ADAMTS2):c.471C>G (p.Tyr157Ter)]

NM_014244.5(ADAMTS2):c.471C>G (p.Tyr157Ter)

Gene:

ADAMTS2:ADAM metallopeptidase with thrombospondin type 1 motif 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_014244.5(ADAMTS2):c.471C>G (p.Tyr157Ter)

HGVS:

NC_000005.10:g.179343830G>C
NG_023212.3:g.6499C>G
NM_014244.5:c.471C>GMANE SELECT
NM_021599.4:c.471C>G
NP_055059.2:p.Tyr157Ter
NP_067610.1:p.Tyr157Ter
NC_000005.9:g.178770831G>C

Protein change:

Y157*

Molecular consequence:

NM_014244.5:c.471C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_021599.4:c.471C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Ehlers-Danlos syndrome, dermatosparaxis type
Synonyms:: EDS VIIC; Dermatosparaxis; Ehlers-Danlos syndrome type 7C (formerly); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009161; MedGen: C2700425; Orphanet: 1901; OMIM: 225410

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003335506	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 28, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10417273, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003335506

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 28, 2022)

germline

clinical testing

PubMed (2)
[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

Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene.

Colige A, Sieron AL, Li SW, Schwarze U, Petty E, Wertelecki W, Wilcox W, Krakow D, Cohn DH, Reardon W, Byers PH, Lapière CM, Prockop DJ, Nusgens BV.

Am J Hum Genet. 1999 Aug;65(2):308-17.

PubMed [citation]

PMID:: 10417273
PMCID:: PMC1377929

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003335506.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ADAMTS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr157*) in the ADAMTS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADAMTS2 are known to be pathogenic (PMID: 10417273).

#	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 20, 2024

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