NM_152594.3(SPRED1):c.221G>T (p.Cys74Phe) AND Legius syndrome

Clinical significance:Uncertain significance (Last evaluated: May 23, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000547389.1

Allele description [Variation Report for NM_152594.3(SPRED1):c.221G>T (p.Cys74Phe)]

NM_152594.3(SPRED1):c.221G>T (p.Cys74Phe)

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.221G>T (p.Cys74Phe)
HGVS:
  • NC_000015.10:g.38322254G>T
  • NG_008980.1:g.74404G>T
  • NM_152594.3:c.221G>TMANE SELECT
  • NP_689807.1:p.Cys74Phe
  • NC_000015.9:g.38614455G>T
  • NM_152594.2:c.221G>T
Protein change:
C74F
Links:
dbSNP: rs1412213561
NCBI 1000 Genomes Browser:
rs1412213561
Molecular consequence:
  • NM_152594.3:c.221G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000645820Invitaecriteria provided, single submitter
Uncertain significance
(May 23, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000645820.1

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

Description

This sequence change replaces cysteine with phenylalanine at codon 74 of the SPRED1 protein (p.Cys74Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with multiple cafe au lait macules with freckling. This individual's mother also carried this variant but was unaffected with any pigmentary lesions or other signs of neurofibromatosis type 1 (PMID: 19920235). Experimental studies have shown that this missense change behaved similarly to wildtype in assays measuring cellular differentiation, neurite outgrowth, Elk-1 and ERK suppression, and binding to the GAP-related domain (GRD) of neurofibromin (PMID: 19920235, 26635368). In summary, this variant is a rare missense change that does not affect protein function in vitro. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

Support Center