NM_152594.3(SPRED1):c.923_924del (p.Ser308fs) AND Legius syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 13, 2019
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:: RCV000543442.10

Allele description [Variation Report for NM_152594.3(SPRED1):c.923_924del (p.Ser308fs)]

NM_152594.3(SPRED1):c.923_924del (p.Ser308fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_152594.3(SPRED1):c.923_924del (p.Ser308fs)

HGVS:

NC_000015.10:g.38351250CT[1]
NG_008980.1:g.103400CT[1]
NM_152594.3:c.923_924delMANE SELECT
NP_689807.1:p.Ser308fs
NC_000015.9:g.38643451CT[1]
NC_000015.9:g.38643451_38643452del
NM_152594.2:c.923_924del
NM_152594.2:c.923_924delCT

Protein change:

S308fs

Links:

dbSNP: rs1555392759

NCBI 1000 Genomes Browser:

rs1555392759

Molecular consequence:

NM_152594.3:c.923_924del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000645828	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 13, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19920235, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000645828

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 13, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome.

Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, et al.

JAMA. 2009 Nov 18;302(19):2111-8. doi: 10.1001/jama.2009.1663. Erratum in: JAMA. 2010 Jun 23;303(24):2477.

PubMed [citation]

PMID:: 19920235

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000645828.6

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

Description

For these reasons, this variant has been classified as Pathogenic. A different frameshift mutation, c.1149_1152del (p.Gly385Ilefs*20), downstream of this variant has been observed in individuals and families with Legius syndrome (PMID:¬†17704776, 21089071), which suggests a truncation in the last exon disrupts SPRED1 function and causes disease. This variant has been reported in two individuals from the same family affected with neurofibromatosis type 1-like syndrome (NFLS), also known as Legius syndrome (PMID: 19920235).¬†ClinVar contains an entry for this variant (Variation ID:¬†468800). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the SPRED1 gene (p.Ser308Cysfs*4). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 137 amino acids of the SPRED1 protein.

#	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: Sep 29, 2024

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