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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 21, 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:: RCV002341433.2

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)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002643602	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 21, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28454995, 29620724 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002643602

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 21, 2022)

germline

clinical testing

PubMed (2)
[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

A multicenter clinical exome study in unselected cohorts from a consanguineous population of Saudi Arabia demonstrated a high diagnostic yield.

Alfares A, Alfadhel M, Wani T, Alsahli S, Alluhaydan I, Al Mutairi F, Alothaim A, Albalwi M, Al Subaie L, Alturki S, Al-Twaijri W, Alrifai M, Al-Rumayya A, Alameer S, Faqeeh E, Alasmari A, Alsamman A, Tashkandia S, Alghamdi A, Alhashem A, Tabarki B, AlShahwan S, et al.

Mol Genet Metab. 2017 Jun;121(2):91-95. doi: 10.1016/j.ymgme.2017.04.002. Epub 2017 Apr 7. No abstract available.

PubMed [citation]

PMID:: 28454995

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

Details of each submission

From Ambry Genetics, SCV002643602.2

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

Description

The p.R169H variant (also known as c.506G>A), located in coding exon 5 of the EFEMP2 gene, results from a G to A substitution at nucleotide position 506. The arginine at codon 169 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in a homozygous state in a subject with muscle weakness (Alfares A et al. Mol. Genet. Metab., 2017 06;121:91-95). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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