NM_020631.5(PLEKHG5):c.1469A>G (p.Lys490Arg) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Feb 10, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000481782.1

Allele description [Variation Report for NM_020631.5(PLEKHG5):c.1469A>G (p.Lys490Arg)]

NM_020631.5(PLEKHG5):c.1469A>G (p.Lys490Arg)

Gene:
PLEKHG5:pleckstrin homology and RhoGEF domain containing G5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.31
Genomic location:
Preferred name:
NM_020631.5(PLEKHG5):c.1469A>G (p.Lys490Arg)
HGVS:
  • NC_000001.11:g.6470808T>C
  • NG_007978.1:g.54202A>G
  • NG_029910.1:g.388A>G
  • NM_001042663.2:c.1637A>G
  • NM_001042664.1:c.1469A>G
  • NM_001042665.1:c.1469A>G
  • NM_001265592.1:c.1706A>G
  • NM_001265593.1:c.1676A>G
  • NM_001265594.2:c.1469A>G
  • NM_020631.5:c.1469A>G
  • NM_198681.3:c.1700A>G
  • NP_001036128.1:p.Lys546Arg
  • NP_001036129.1:p.Lys490Arg
  • NP_001036130.1:p.Lys490Arg
  • NP_001252521.1:p.Lys569Arg
  • NP_001252522.1:p.Lys559Arg
  • NP_001252523.1:p.Lys490Arg
  • NP_065682.2:p.Lys490Arg
  • NP_941374.2:p.Lys567Arg
  • LRG_262:g.54202A>G
  • NC_000001.10:g.6530868T>C
  • NM_020631.4:c.1469A>G
Protein change:
K490R
Links:
dbSNP: rs534760199
NCBI 1000 Genomes Browser:
rs534760199
Molecular consequence:
  • NM_001042663.2:c.1637A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042664.1:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042665.1:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265592.1:c.1706A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265593.1:c.1676A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265594.2:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020631.5:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198681.3:c.1700A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000572979GeneDxcriteria provided, single submitter
Uncertain significance
(Feb 10, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000572979.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.1469 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1469 A>G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Multiple in-silico splice prediction models predict that c.1469 A>G creates a cryptic splice donor site which may supplant the natural donor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies the actual effect of c.1469 A>G on splicing in this individual is unknown. If c.1469 A>G does not alter splicing, it will result in the K490R missense change. The K490R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.

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

Last Updated: Feb 27, 2021

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