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:
current
Accession:
RCV000001887.4

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

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

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.637C>T (p.Gln213Ter)
HGVS:
  • 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
Links:
OMIM: 609291.0006; dbSNP: rs121434316
NCBI 1000 Genomes Browser:
rs121434316
Molecular consequence:
  • NM_152594.3:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000022043OMIMno assertion criteria providedPathogenic
(Jul 1, 2009)
germlineliterature only

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

SCV000942975Invitaecriteria provided, single submitter
Pathogenic
(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

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 OMIM, SCV000022043.2

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

Description

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.

#SampleMethodObservation
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)

Description

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.

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

Last Updated: Nov 27, 2021

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