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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 30, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000001887.9

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
Synonyms:: Neurofibromatosis type 1 like syndrome
Identifiers:: MONDO: MONDO:0012669; MedGen: C1969623; Orphanet: 137605; OMIM: 611431

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022043	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2009)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000942975	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 30, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17704776, 19366998, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000022043

OMIM

no assertion criteria provided

Pathogenic
(Jul 1, 2009)

germline

literature only

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

SCV000942975

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 30, 2018)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype.

Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E.

Nat Genet. 2007 Sep;39(9):1120-6. Epub 2007 Aug 19.

PubMed [citation]

PMID:: 17704776

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 (3)

Details of each submission

From OMIM, SCV000022043.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV000942975.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SPRED1 are known to be pathogenic (PMID: 17704776). 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). This variant is not present in population databases (ExAC no frequency). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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