NM_152594.3(SPRED1):c.32+2T>G AND Legius syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 12, 2022
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:: RCV002011666.4

Allele description [Variation Report for NM_152594.3(SPRED1):c.32+2T>G]

NM_152594.3(SPRED1):c.32+2T>G

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.32+2T>G

HGVS:

NC_000015.10:g.38253219T>G
NG_008980.1:g.5369T>G
NM_152594.3:c.32+2T>GMANE SELECT
NC_000015.9:g.38545420T>G

Links:

dbSNP: rs2140943462

NCBI 1000 Genomes Browser:

rs2140943462

Molecular consequence:

NM_152594.3:c.32+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

Recent activity

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Klebsiella pneumoniae strain KLP00014, whole genome shotgun sequencing project
Klebsiella pneumoniae strain KLP00014, whole genome shotgun sequencing project
gi|2577542546|gb|LGPP00000000.1|LGP 0000

Nucleotide
Klebsiella pneumoniae strain KLP00034, whole genome shotgun sequencing project
Klebsiella pneumoniae strain KLP00034, whole genome shotgun sequencing project
gi|2577542555|gb|LGPR00000000.1|LGP 0000

Nucleotide
lysosomal amino acid transporter 1 homolog isoform X2 [Homo sapiens]
lysosomal amino acid transporter 1 homolog isoform X2 [Homo sapiens]
gi|2462510521|ref|XP_054193223.1|

Protein
RNA export factor GLE2 [Saccharomyces cerevisiae S288C]
RNA export factor GLE2 [Saccharomyces cerevisiae S288C]
gi|398364677|ref|NP_011033.3|

Protein
Cardamine barbaraeoides
Cardamine barbaraeoides
Phylogenomics of Balkan Cardamine

BioProject

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002298860	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 12, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 17704776, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002298860

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 12, 2022)

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002298860.3

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

Description

This sequence change affects a donor splice site in intron 1 of the SPRED1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SPRED1 are known to be pathogenic (PMID: 17704776). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPRED1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1510307). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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

ClinVar

Relating variation to medicine