NM_152594.3(SPRED1):c.842A>G (p.Gln281Arg) AND Legius syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 29, 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:: RCV000645299.8

Allele description [Variation Report for NM_152594.3(SPRED1):c.842A>G (p.Gln281Arg)]

NM_152594.3(SPRED1):c.842A>G (p.Gln281Arg)

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.842A>G (p.Gln281Arg)

HGVS:

NC_000015.10:g.38351171A>G
NG_008980.1:g.103321A>G
NM_152594.3:c.842A>GMANE SELECT
NP_689807.1:p.Gln281Arg
NC_000015.9:g.38643372A>G
NM_152594.2:c.842A>G

Protein change:

Q281R

Links:

dbSNP: rs1427402192

NCBI 1000 Genomes Browser:

rs1427402192

Molecular consequence:

NM_152594.3:c.842A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Legius syndrome
Synonyms:: Neurofibromatosis type 1 like syndrome
Identifiers:: MONDO: MONDO:0012669; MedGen: C1969623; Orphanet: 137605; OMIM: 611431

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000767042	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 29, 2023)	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

SCV000767042

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 29, 2023)

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

Citations

PubMed

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000767042.6

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

Description

This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 281 of the SPRED1 protein (p.Gln281Arg). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SPRED1-related conditions. ClinVar contains an entry for this variant (Variation ID: 536691). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt SPRED1 function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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: Mar 5, 2024

ClinVar

Relating variation to medicine