NM_152594.3(SPRED1):c.637C>T (p.Gln213Ter) AND Legius syndrome

Clinical significance:Pathogenic (Last evaluated: Oct 30, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_152594.3(SPRED1):c.637C>T (p.Gln213Ter)]

NM_152594.3(SPRED1):c.637C>T (p.Gln213Ter)

SPRED1:sprouty related EVH1 domain containing 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_152594.3(SPRED1):c.637C>T (p.Gln213Ter)
  • NC_000015.10:g.38349476C>T
  • NG_008980.1:g.101626C>T
  • NM_152594.3:c.637C>TMANE SELECT
  • NP_689807.1:p.Gln213Ter
  • NC_000015.9:g.38641677C>T
  • NM_152594.2:c.637C>T
Protein change:
Q213*; GLN213TER
OMIM: 609291.0006; dbSNP: rs121434316
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_152594.3:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]


Legius syndrome (LGSS)
Neurofibromatosis type 1 like syndrome
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)
SCV000022043OMIMno assertion criteria providedPathogenic
(Jul 1, 2009)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000942975Invitaecriteria provided, single submitter
(Oct 30, 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
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



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]

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]

Details of each submission

From OMIM, SCV000022043.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)


In affected members of a French family with Legius syndrome (LGSS; 611431), Pasmant et al. (2009) identified a heterozygous 637C-T transition in exon 7 of the SPRED1 gene, resulting in a gln213-to-ter (Q213X) substitution. The phenotype included a high prevalence of cafe-au-lait spots and axillary and groin freckling. One patient had a learning disability. None had neurofibromas or Lisch nodules.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000942975.1

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


This sequence change creates a premature translational stop signal (p.Gln213*) in the SPRED1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Legius syndrome in a family (PMID: 19366998). ClinVar contains an entry for this variant (Variation ID: 1814). Loss-of-function variants in SPRED1 are known to be pathogenic (PMID: 17704776). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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