NM_152594.3(SPRED1):c.190C>T (p.Arg64Ter) AND Legius syndrome

Clinical significance:Pathogenic (Last evaluated: Aug 4, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000001886.6

Allele description [Variation Report for NM_152594.3(SPRED1):c.190C>T (p.Arg64Ter)]

NM_152594.3(SPRED1):c.190C>T (p.Arg64Ter)

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.190C>T (p.Arg64Ter)
HGVS:
  • NC_000015.10:g.38299530C>T
  • NG_008980.1:g.51680C>T
  • NM_152594.3:c.190C>TMANE SELECT
  • NP_689807.1:p.Arg64Ter
  • NC_000015.9:g.38591731C>T
  • NM_152594.2:c.190C>T
Protein change:
R64*; ARG64TER
Links:
OMIM: 609291.0005; dbSNP: rs121434315
NCBI 1000 Genomes Browser:
rs121434315
Molecular consequence:
  • NM_152594.3:c.190C>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
SCV000022042OMIMno assertion criteria providedPathogenic
(Jul 1, 2009)
germlineliterature only

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

SCV000782323Center for Human Genetics, Inc,Center for Human Genetics, Inccriteria provided, single submitter
Pathogenic
(Nov 1, 2016)
germlineclinical testing

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

SCV000833323Invitaecriteria provided, single submitter
Pathogenic
(Aug 4, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

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
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000022042.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In an individual with Legius syndrome (LGSS; 611431), Brems et al. (2007) identified a heterozygous 190C-T transition in exon 3 of the SPRED1 gene, resulting in an arg64-to-ter (R64X) substitution. The patient had multiple cafe-au-lait spots and did not have a NF1 mutation.

In affected members of a French family with Legius syndrome, Pasmant et al. (2009) identified the same R64X mutation. The phenotype included a high prevalence of cafe-au-lait spots and axillary and groin freckling. Two patients had a lipoma and another had learning disability. None had neurofibromas or Lisch nodules.

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

From Center for Human Genetics, Inc,Center for Human Genetics, Inc, SCV000782323.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000833323.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg64*) 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 one family (PMID: 19366998). ClinVar contains an entry for this variant (Variation ID: 1813). 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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