NM_152594.3(SPRED1):c.1103G>C (p.Cys368Ser) AND Legius syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 24, 2020
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:: RCV001370671.7

Allele description [Variation Report for NM_152594.3(SPRED1):c.1103G>C (p.Cys368Ser)]

NM_152594.3(SPRED1):c.1103G>C (p.Cys368Ser)

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.1103G>C (p.Cys368Ser)

HGVS:

NC_000015.10:g.38351432G>C
NG_008980.1:g.103582G>C
NM_152594.3:c.1103G>CMANE SELECT
NP_689807.1:p.Cys368Ser
NC_000015.9:g.38643633G>C
NM_152594.2:c.1103G>C

Protein change:

C368S

Links:

dbSNP: rs2141016537

NCBI 1000 Genomes Browser:

rs2141016537

Molecular consequence:

NM_152594.3:c.1103G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001567197	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 24, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31573083, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001567197

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 24, 2020)

germline

clinical testing

PubMed (2)
[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

Mutational spectrum by phenotype: panel-based NGS testing of patients with clinical suspicion of RASopathy and children with multiple café-au-lait macules.

Castellanos E, Rosas I, Negro A, Gel B, Alibés A, Baena N, Pineda M, Pi G, Pintos G, Salvador H, Lázaro C, Blanco I, Vilageliu L, Brems H, Grinberg D, Legius E, Serra E.

Clin Genet. 2020 Feb;97(2):264-275. doi: 10.1111/cge.13649. Epub 2019 Dec 12.

PubMed [citation]

PMID:: 31573083

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001567197.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces cysteine with serine at codon 368 of the SPRED1 protein (p.Cys368Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with multiple caf√©-au-lait macules (PMID: 31573083). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Jun 23, 2024

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