NM_152594.3(SPRED1):c.1151del (p.Glu384fs) AND Legius syndrome

Clinical significance:Pathogenic (Last evaluated: Nov 8, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000795942.1

Allele description [Variation Report for NM_152594.3(SPRED1):c.1151del (p.Glu384fs)]

NM_152594.3(SPRED1):c.1151del (p.Glu384fs)

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.1151del (p.Glu384fs)
HGVS:
  • NC_000015.10:g.38351480del
  • NG_008980.1:g.103630del
  • NM_152594.3:c.1151delMANE SELECT
  • NP_689807.1:p.Glu384fs
  • NC_000015.9:g.38643681del
  • NM_152594.2:c.1151delA
Protein change:
E384fs
Links:
dbSNP: rs1595763928
NCBI 1000 Genomes Browser:
rs1595763928
Molecular consequence:
  • NM_152594.3:c.1151del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000935423Invitaecriteria provided, single submitter
Pathogenic
(Nov 8, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Distinct requirements for the Sprouty domain for functional activity of Spred proteins.

King JA, Straffon AF, D'Abaco GM, Poon CL, I ST, Smith CM, Buchert M, Corcoran NM, Hall NE, Callus BA, Sarcevic B, Martin D, Lock P, Hovens CM.

Biochem J. 2005 Jun 1;388(Pt 2):445-54.

PubMed [citation]
PMID:
15683364
PMCID:
PMC1138951

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, SCV000935423.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change results in a premature translational stop signal in the SPRED1 gene (p.Glu384Glyfs*22). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 61 amino acids of the SPRED1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SPRED1-related disease. While experimental studies have not been performed on this particular variant, it is expected to disrupt the Sprouty domain of the SPRED1 protein which is necessary for proper function of the SPRED1 protein (PMID: 15683364). This variant disrupts the C-terminus of the SPRED1 protein. Other variant(s) that disrupt this region (p.Cys418Alafs*6, p.Met417Ttrfs*15, p.Arg403Leufs*30) have been determined to be pathogenic (PMID: 19920235). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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