NM_016938.5(EFEMP2):c.506G>A (p.Arg169His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 1, 2024
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:: RCV004767376.1

Allele description [Variation Report for NM_016938.5(EFEMP2):c.506G>A (p.Arg169His)]

NM_016938.5(EFEMP2):c.506G>A (p.Arg169His)

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.506G>A (p.Arg169His)

HGVS:

NC_000011.10:g.65870222C>T
NG_012304.2:g.7713G>A
NM_016938.5:c.506G>AMANE SELECT
NP_058634.4:p.Arg169His
NC_000011.9:g.65637693C>T
NM_016938.4:c.506G>A
NR_037718.2:n.631G>A

Protein change:

R169H

Links:

dbSNP: rs141310608

NCBI 1000 Genomes Browser:

rs141310608

Molecular consequence:

NM_016938.5:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_037718.2:n.631G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005381611	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Aug 1, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31127727, 29620724, 28454995 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005381611

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Aug 1, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Panel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service.

Westra D, Schouten MI, Stunnenberg BC, Kusters B, Saris CGJ, Erasmus CE, van Engelen BG, Bulk S, Verschuuren-Bemelmans CC, Gerkes EH, de Geus C, van der Zwaag PA, Chan S, Chung B, Barge-Schaapveld DQCM, Kriek M, Sznajer Y, van Spaendonck-Zwarts K, van der Kooi AJ, Krause A, Schönewolf-Greulich B, de Die-Smulders C, et al.

J Neuromuscul Dis. 2019;6(2):241-258. doi: 10.3233/JND-180376.

PubMed [citation]

PMID:: 31127727

Expanding the phenome and variome of skeletal dysplasia.

Maddirevula S, Alsahli S, Alhabeeb L, Patel N, Alzahrani F, Shamseldin HE, Anazi S, Ewida N, Alsaif HS, Mohamed JY, Alazami AM, Ibrahim N, Abdulwahab F, Hashem M, Abouelhoda M, Monies D, Al Tassan N, Alshammari M, Alsagheir A, Seidahmed MZ, Sogati S, Aglan MS, et al.

Genet Med. 2018 Dec;20(12):1609-1616. doi: 10.1038/gim.2018.50. Epub 2018 Apr 5.

PubMed [citation]

PMID:: 29620724

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005381611.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: EFEMP2 c.506G>A (p.Arg169His) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 250720 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in EFEMP2 causing Autosomal Recessive Cutis Laxa (9.6e-05 vs 0.00071), allowing no conclusion about variant significance. c.506G>A has been reported in the literature in homozygous individuals affected with features of Autosomal Recessive Cutis Laxa and/or with features of musculoskeletal disorders (Alfares_2017, Maddirevula_2018, Westra_2019). These reports do not provide unequivocal conclusions about association of the variant with Autosomal Recessive Cutis Laxa. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28454995, 29620724, 31127727). ClinVar contains an entry for this variant (Variation ID: 472828). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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 1, 2025

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