NM_152594.3(SPRED1):c.3G>A (p.Met1Ile) AND Legius syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jan 14, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001059001.2

Allele description [Variation Report for NM_152594.3(SPRED1):c.3G>A (p.Met1Ile)]

NM_152594.3(SPRED1):c.3G>A (p.Met1Ile)

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.3G>A (p.Met1Ile)
HGVS:
  • NC_000015.10:g.38253188G>A
  • NG_008980.1:g.5338G>A
  • NM_152594.3:c.3G>AMANE SELECT
  • NP_689807.1:p.Met1Ile
  • NC_000015.9:g.38545389G>A
  • NM_152594.2:c.3G>A
Protein change:
M1I
Links:
dbSNP: rs1324903101
NCBI 1000 Genomes Browser:
rs1324903101
Molecular consequence:
  • NM_152594.3:c.3G>A - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_152594.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001223604Invitaecriteria provided, single submitter
Likely pathogenic
(Jan 14, 2019)
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

SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.

Pasmant E, Sabbagh A, Hanna N, Masliah-Planchon J, Jolly E, Goussard P, Ballerini P, Cartault F, Barbarot S, Landman-Parker J, Soufir N, Parfait B, Vidaud M, Wolkenstein P, Vidaud D, France RN.

J Med Genet. 2009 Jul;46(7):425-30. doi: 10.1136/jmg.2008.065243. Epub 2009 Apr 14.

PubMed [citation]
PMID:
19366998

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, SCV001223604.2

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

Description

This sequence change affects the initiator methionine of the SPRED1 mRNA. The next in-frame methionine is located at codon 22. This variant is not present in population databases (ExAC no frequency). Disruption of the initiator codon has been observed to segregate with clinical features of Legius syndrome in a family (PMID: 19366998). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 27, 2021

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