NM_020631.6(PLEKHG5):c.1469A>G (p.Lys490Arg) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 10, 2017
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:: RCV000481782.1

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.1469A>G (p.Lys490Arg)]

NM_020631.6(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_020631.6(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_001042663.3:c.1580A>G
NM_001042664.2:c.1469A>G
NM_001042665.2:c.1469A>G
NM_001265592.2:c.1580A>G
NM_001265593.2:c.1676A>G
NM_001265594.3:c.1469A>G
NM_020631.6:c.1469A>GMANE SELECT
NM_198681.4:c.1469A>G
NP_001036128.2:p.Lys527Arg
NP_001036129.1:p.Lys490Arg
NP_001036129.1:p.Lys490Arg
NP_001036130.1:p.Lys490Arg
NP_001036130.1:p.Lys490Arg
NP_001252521.2:p.Lys527Arg
NP_001252522.1:p.Lys559Arg
NP_001252522.1:p.Lys559Arg
NP_001252523.1:p.Lys490Arg
NP_001252523.1:p.Lys490Arg
NP_065682.2:p.Lys490Arg
NP_065682.2:p.Lys490Arg
NP_941374.3:p.Lys490Arg
LRG_262t1:c.1469A>G
LRG_262:g.54202A>G
LRG_262p1:p.Lys490Arg
NC_000001.10:g.6530868T>C
NM_001042664.1:c.1469A>G
NM_001042665.1:c.1469A>G
NM_001265593.1:c.1676A>G
NM_001265594.2:c.1469A>G
NM_020631.3:c.1469A>G
NM_020631.4:c.1469A>G

Protein change:

K490R

Links:

dbSNP: rs534760199

NCBI 1000 Genomes Browser:

rs534760199

Molecular consequence:

NM_001042663.3:c.1580A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042664.2:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042665.2:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265592.2:c.1580A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265593.2:c.1676A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265594.3:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020631.6:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198681.4:c.1469A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000572979	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Feb 10, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000572979

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Feb 10, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000572979.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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