NM_014244.5(ADAMTS2):c.2226T>A (p.Phe742Leu) AND Ehlers-Danlos syndrome, dermatosparaxis type

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 11, 2020
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:: RCV001825232.6

Allele description [Variation Report for NM_014244.5(ADAMTS2):c.2226T>A (p.Phe742Leu)]

NM_014244.5(ADAMTS2):c.2226T>A (p.Phe742Leu)

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.2226T>A (p.Phe742Leu)

HGVS:

NC_000005.10:g.179132294A>T
NG_023212.3:g.218035T>A
NM_014244.5:c.2226T>AMANE SELECT
NP_055059.2:p.Phe742Leu
NC_000005.9:g.178559295A>T
NM_014244.4:c.2226T>A

Protein change:

F742L

Links:

dbSNP: rs768906337

NCBI 1000 Genomes Browser:

rs768906337

Molecular consequence:

NM_014244.5:c.2226T>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002074983	GenomeConnect, ClinGen	no classification provided	not provided	unknown	phenotyping only
SCV002196778	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 11, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002074983

GenomeConnect, ClinGen

no classification provided

not provided

unknown

phenotyping only

SCV002196778

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 11, 2020)

germline

clinical testing

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

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	phenotyping only

Citations

PubMed

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 GenomeConnect, ClinGen, SCV002074983.1

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

Description

Variant interpreted as Uncertain significance and reported on 11-10-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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

From Invitae, SCV002196778.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with ADAMTS2-related conditions. This variant is present in population databases (rs768906337, ExAC 0.02%). This sequence change replaces phenylalanine with leucine at codon 742 of the ADAMTS2 protein (p.Phe742Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine.

#	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: Mar 5, 2024

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