NM_152594.3(SPRED1):c.1015C>T (p.Gln339Ter) AND Legius syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 4, 2021
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:: RCV001862131.4

Allele description [Variation Report for NM_152594.3(SPRED1):c.1015C>T (p.Gln339Ter)]

NM_152594.3(SPRED1):c.1015C>T (p.Gln339Ter)

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.1015C>T (p.Gln339Ter)

HGVS:

NC_000015.10:g.38351344C>T
NG_008980.1:g.103494C>T
NM_152594.3:c.1015C>TMANE SELECT
NP_689807.1:p.Gln339Ter
NC_000015.9:g.38643545C>T

Protein change:

Q339*

Links:

dbSNP: rs1566876895

NCBI 1000 Genomes Browser:

rs1566876895

Molecular consequence:

NM_152594.3:c.1015C>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
SCV002143640	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 4, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17704776, 21089071, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002143640

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 4, 2021)

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	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

Legius syndrome in fourteen families.

Denayer E, Chmara M, Brems H, Kievit AM, van Bever Y, Van den Ouweland AM, Van Minkelen R, de Goede-Bolder A, Oostenbrink R, Lakeman P, Beert E, Ishizaki T, Mori T, Keymolen K, Van den Ende J, Mangold E, Peltonen S, Brice G, Rankin J, Van Spaendonck-Zwarts KY, Yoshimura A, Legius E.

Hum Mutat. 2011 Jan;32(1):E1985-98. doi: 10.1002/humu.21404.

PubMed [citation]

PMID:: 21089071
PMCID:: PMC3038325

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002143640.3

#	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. This variant disrupts a region of the SPRED1 protein in which other variant(s) (p.Gly385Ilefs*20) have been determined to be pathogenic (PMID: 17704776, 21089071). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 592540). This variant has not been reported in the literature in individuals affected with SPRED1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln339*) in the SPRED1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 106 amino acid(s) of the SPRED1 protein.

#	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: Sep 29, 2024

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