NM_152594.3(SPRED1):c.903_906del (p.Leu302fs) AND Legius syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 4, 2020
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:: RCV001235430.8

Allele description [Variation Report for NM_152594.3(SPRED1):c.903_906del (p.Leu302fs)]

NM_152594.3(SPRED1):c.903_906del (p.Leu302fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_152594.3(SPRED1):c.903_906del (p.Leu302fs)

HGVS:

NC_000015.10:g.38351232_38351235del
NG_008980.1:g.103382_103385del
NM_152594.3:c.903_906delMANE SELECT
NP_689807.1:p.Leu302fs
NC_000015.9:g.38643432_38643435del
NC_000015.9:g.38643433_38643436del
NM_152594.2:c.903_906del
NM_152594.2:c.903_906delGTTA

Protein change:

L302fs

Links:

dbSNP: rs1595763662

NCBI 1000 Genomes Browser:

rs1595763662

Molecular consequence:

NM_152594.3:c.903_906del - 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
SCV001408115	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 4, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17704776, 25883013, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001408115

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 4, 2020)

germline

clinical testing

PubMed (3)
[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

Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype.

Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E.

Nat Genet. 2007 Sep;39(9):1120-6. Epub 2007 Aug 19.

PubMed [citation]

PMID:: 17704776

Legius syndrome: case report and review of literature.

Benelli E, Bruno I, Belcaro C, Ventura A, Berti I.

Ital J Pediatr. 2015 Feb 8;41:8. doi: 10.1186/s13052-015-0115-9. Review.

PubMed [citation]

PMID:: 25883013
PMCID:: PMC4323213

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001408115.5

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

Description

This sequence change results in a premature translational stop signal in the SPRED1 gene (p.Leu302Valfs*16). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 143 amino acids of the SPRED1 protein. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SPRED1 protein. Other variant(s) that disrupt this region (p.Arg325*) have been determined to be pathogenic (PMID: 17704776, 25883013). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with SPRED1-related conditions. ClinVar contains an entry for this variant (Variation ID: 817884).

#	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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