NM_152594.3(SPRED1):c.71G>A (p.Arg24Gln) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 20, 2017
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:: RCV002374619.2

Allele description [Variation Report for NM_152594.3(SPRED1):c.71G>A (p.Arg24Gln)]

NM_152594.3(SPRED1):c.71G>A (p.Arg24Gln)

Gene:

SPRED1:sprouty related EVH1 domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_152594.3(SPRED1):c.71G>A (p.Arg24Gln)

HGVS:

NC_000015.10:g.38299411G>A
NG_008980.1:g.51561G>A
NM_152594.3:c.71G>AMANE SELECT
NP_689807.1:p.Arg24Gln
NC_000015.9:g.38591612G>A
NM_152594.2:c.71G>A

Protein change:

R24Q

Links:

dbSNP: rs1057518150

NCBI 1000 Genomes Browser:

rs1057518150

Molecular consequence:

NM_152594.3:c.71G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002670174	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jan 20, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21548021, 26635368 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002670174

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jan 20, 2017)

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

Identification of SPRED1 deletions using RT-PCR, multiplex ligation-dependent probe amplification and quantitative PCR.

Spencer E, Davis J, Mikhail F, Fu C, Vijzelaar R, Zackai EH, Feret H, Meyn MS, Shugar A, Bellus G, Kocsis K, Kivirikko S, Pöyhönen M, Messiaen L.

Am J Med Genet A. 2011 Jun;155A(6):1352-9. doi: 10.1002/ajmg.a.33894. Epub 2011 May 5.

PubMed [citation]

PMID:: 21548021

Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1.

Hirata Y, Brems H, Suzuki M, Kanamori M, Okada M, Morita R, Llano-Rivas I, Ose T, Messiaen L, Legius E, Yoshimura A.

J Biol Chem. 2016 Feb 12;291(7):3124-34. doi: 10.1074/jbc.M115.703710. Epub 2015 Dec 3.

PubMed [citation]

PMID:: 26635368
PMCID:: PMC4751360

Details of each submission

From Ambry Genetics, SCV002670174.2

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

Description

The p.R24Q variant (also known as c.71G>A), located in coding exon 2 of the SPRED1 gene, results from a G to A substitution at nucleotide position 71. The arginine at codon 24 is replaced by glutamine, an amino acid with highly similar properties. This variant has been reported in multiple individuals without NF1 mutations who presented with a Legius syndrome phenotype. This variant has shown strong segregation with the clinical presentation of multiple café-au-lait macules (Spencer E et al, Am. J. Med. Genet. A 2011 Jun; 155A(6):1352-9; Hirata Y et al, J. Biol. Chem. 2016 Feb; 291(7):3124-34). By in vitro assays, this variant was suggested to partially reduce the interaction between SPRED1 EVH1 and NF1 GRD domains, and to relieve the SPRED1 suppression on ERK activity to a limited extent (Hirata Y et al, J. Biol. Chem. 2016 Feb; 291(7):3124-34). This variant was not reported in the ExAC database, with coverage at this position. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Oct 8, 2024

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