NM_016938.5(EFEMP2):c.608A>C (p.Asp203Ala) AND Cutis laxa, autosomal recessive, type 1B

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Aug 24, 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:: RCV000034873.9

Allele description [Variation Report for NM_016938.5(EFEMP2):c.608A>C (p.Asp203Ala)]

NM_016938.5(EFEMP2):c.608A>C (p.Asp203Ala)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_016938.5(EFEMP2):c.608A>C (p.Asp203Ala)

HGVS:

NC_000011.10:g.65869976T>G
NG_012304.2:g.7959A>C
NM_016938.5:c.608A>CMANE SELECT
NP_058634.4:p.Asp203Ala
NC_000011.9:g.65637447T>G
NM_016938.4:c.608A>C
NR_037718.2:n.733A>C

Protein change:

D203A; ASP203ALA

Links:

OMIM: 604633.0009; dbSNP: rs193302864

NCBI 1000 Genomes Browser:

rs193302864

Molecular consequence:

NM_016938.5:c.608A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_037718.2:n.733A>C - 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
SCV000058479	OMIM	no assertion criteria provided	Pathogenic (Sep 3, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002024468	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 24, 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

SCV000058479

OMIM

no assertion criteria provided

Pathogenic
(Sep 3, 2012)

germline

literature only

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

SCV002024468

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 24, 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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis.

Kappanayil M, Nampoothiri S, Kannan R, Renard M, Coucke P, Malfait F, Menon S, Ravindran HK, Kurup R, Faiyaz-Ul-Haque M, Kumar K, De Paepe A.

Orphanet J Rare Dis. 2012 Sep 3;7:61. doi: 10.1186/1750-1172-7-61.

PubMed [citation]

PMID:: 22943132
PMCID:: PMC3598868

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 OMIM, SCV000058479.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 21 patients, 11 male and 10 female, with autosomal recessive cutis laxa type 1B (ARCL1B; 614437), Kappanayil et al. (2012) identified homozygosity for an A-to-C transversion at nucleotide 608 in exon 7 of the EFEMP2 gene that resulted in an aspartic acid-to-alanine substitution at codon 203 (D203A). All patients were Muslims from the Mappila community of the Malabar region of the Indian state of Kerala; 8 came from consanguineous families. All parents tested were normal and carried this mutation in heterozygosity. Homozygosity was lethal in 17 of the 21 patients, who died at a median age of 4 months. In another patient from the same community, Kappanayil et al. (2012) detected compound heterozygosity for this mutation and a de novo missense mutation (604633.0010).

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

From Revvity Omics, Revvity, SCV002024468.3

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

#	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: Jun 29, 2024

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