NM_016938.5(EFEMP2):c.919_952dup (p.Pro318fs) AND Cutis laxa, autosomal recessive, type 1B

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 10, 2023
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:: RCV001382781.5

Allele description [Variation Report for NM_016938.5(EFEMP2):c.919_952dup (p.Pro318fs)]

NM_016938.5(EFEMP2):c.919_952dup (p.Pro318fs)

Gene:

EFEMP2:EGF containing fibulin extracellular matrix protein 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_016938.5(EFEMP2):c.919_952dup (p.Pro318fs)

HGVS:

NC_000011.10:g.65868319_65868352dup
NG_012304.2:g.9585_9618dup
NG_053116.1:g.13258_13291dup
NM_016938.5:c.919_952dupMANE SELECT
NP_058634.4:p.Pro318fs
NC_000011.9:g.65635787_65635788insGCTCCACGCAGCGGTTGGTGTCCACGCAGCGGTA
NC_000011.9:g.65635790_65635823dup
NR_037718.2:n.1044_1077dup

Protein change:

P318fs

Links:

dbSNP: rs2134747667

NCBI 1000 Genomes Browser:

rs2134747667

Molecular consequence:

NM_016938.5:c.919_952dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_037718.2:n.1044_1077dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cutis laxa, autosomal recessive, type 1B (ARCL1B)
Synonyms:: CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB
Identifiers:: MONDO: MONDO:0013754; MedGen: C3280798; Orphanet: 90349; OMIM: 614437

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001581686	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 10, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17937443, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581686

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 10, 2023)

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

Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.

Dasouki M, Markova D, Garola R, Sasaki T, Charbonneau NL, Sakai LY, Chu ML.

Am J Med Genet A. 2007 Nov 15;143A(22):2635-41.

PubMed [citation]

PMID:: 17937443

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001581686.4

#	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. ClinVar contains an entry for this variant (Variation ID: 1070589). This variant has not been reported in the literature in individuals affected with EFEMP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro318Leufs*18) in the EFEMP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EFEMP2 are known to be pathogenic (PMID: 17937443).

#	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: Sep 29, 2024

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