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NM_005842.4(SPRY2):c.355C>T (p.Arg119Trp) AND IgA nephropathy, susceptibility to, 3

Germline classification:
risk factor (1 submission)
Last evaluated:
Sep 18, 2019
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000207508.5

Allele description [Variation Report for NM_005842.4(SPRY2):c.355C>T (p.Arg119Trp)]

NM_005842.4(SPRY2):c.355C>T (p.Arg119Trp)

Gene:
SPRY2:sprouty RTK signaling antagonist 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q31.1
Genomic location:
Preferred name:
NM_005842.4(SPRY2):c.355C>T (p.Arg119Trp)
HGVS:
  • NC_000013.11:g.80337351G>A
  • NG_050650.1:g.8765C>T
  • NM_001318536.1:c.355C>T
  • NM_001318537.1:c.355C>T
  • NM_001318538.1:c.355C>T
  • NM_005842.4:c.355C>TMANE SELECT
  • NP_001305465.1:p.Arg119Trp
  • NP_001305466.1:p.Arg119Trp
  • NP_001305467.1:p.Arg119Trp
  • NP_005833.1:p.Arg119Trp
  • NC_000013.10:g.80911486G>A
  • NM_005842.2:c.355C>T
  • O43597:p.Arg119Trp
Protein change:
R119W; ARG119TRP
Links:
UniProtKB: O43597#VAR_076288; OMIM: 602466.0001; dbSNP: rs869025336
NCBI 1000 Genomes Browser:
rs869025336
Molecular consequence:
  • NM_001318536.1:c.355C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318537.1:c.355C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318538.1:c.355C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005842.4:c.355C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
IgA nephropathy, susceptibility to, 3 (IGAN3)
Identifiers:
MONDO: MONDO:0014786; MedGen: C4225194; OMIM: 616818

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000263036OMIM
no assertion criteria provided
risk factor
(Sep 18, 2019) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy.

Milillo A, La Carpia F, Costanzi S, D'Urbano V, Martini M, Lanuti P, Vischini G, Larocca LM, Marchisio M, Miscia S, Amoroso A, Gurrieri F, Sangiorgi E.

Eur J Hum Genet. 2015 Dec;23(12):1673-8. doi: 10.1038/ejhg.2015.52. Epub 2015 Mar 18.

PubMed [citation]
PMID:
25782674
PMCID:
PMC4795196

Details of each submission

From OMIM, SCV000263036.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In affected members of a large Sicilian family with autosomal dominant IgA nephropathy-3 (IGAN3; 616818), Milillo et al. (2015) identified a heterozygous c.355C-T transition (c.355C-T, NM_005842.2) in the SPRY2 gene, resulting in an arg119-to-trp (R119W) substitution at a highly conserved residue in the N-terminal region close to ser121, which is phosphorylated. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 132), 1000 Genomes Project, or Exome Sequencing Project databases, or in 52 Sicilian controls. It was identified in 3 unaffected family members who were under the age of 20 years, but not in any unaffected family members older than 20 years, consistent with segregation. Patient lymphoblastoid cells showed decreased amounts of SPRY2 mRNA, but normal protein levels resulting from increased stability of the mutant protein; there was no difference in the ratio between phosphorylated and nonphosphorylated forms compared to controls. Patient cells showed downregulation of the MAPK/ERK1/2 pathway. Cells from 2 unrelated patients with IgA nephropathy who did not have SPRY2 mutations also showed downregulation of the MAPK/ERK1/2 pathway, suggesting that it may be a common disease mechanism.

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

Last Updated: Apr 23, 2022