rs201201843

Variant names:

• chr19-39416866-C-A
• rs201201843
• NM_022835.3:c.610C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-39416866-C-A
• chr19-39416866-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022835.3(PLEKHG2):​c.610C>A​(p.Arg204Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLEKHG2 NM_022835.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45

Genes affected

PLEKHG2 (HGNC:29515): (pleckstrin homology and RhoGEF domain containing G2) The protein encoded by this gene is a RhoGTPase that can activate CDC42 by promoting exchange of GDP for GTP on CDC42. The encoded protein is activated by binding to the beta and gamma subunits of heterotrimeric guanine nucleotide-binding protein. Defects in this gene have been associated with leukodystrophy and acquired microcephaly with or without dystonia. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG2	NM_022835.3	c.610C>A	p.Arg204Arg	synonymous_variant	Exon 7 of 19	ENST00000425673.6	NP_073746.2
PLEKHG2	NM_001351693.2	c.433C>A	p.Arg145Arg	synonymous_variant	Exon 7 of 20		NP_001338622.1
PLEKHG2	NM_001351694.2	c.610C>A	p.Arg204Arg	synonymous_variant	Exon 7 of 18		NP_001338623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG2	ENST00000425673.6	c.610C>A	p.Arg204Arg	synonymous_variant	Exon 7 of 19	2	NM_022835.3	ENSP00000392906.2
PLEKHG2	ENST00000205135.8	c.298C>A	p.Arg100Arg	synonymous_variant	Exon 5 of 15	1		ENSP00000205135.3
PLEKHG2	ENST00000458508.6	c.433C>A	p.Arg145Arg	synonymous_variant	Exon 7 of 20	2		ENSP00000408857.2
PLEKHG2	ENST00000409797.6	c.610C>A	p.Arg204Arg	synonymous_variant	Exon 7 of 18	2		ENSP00000386492.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Benign	0.84
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.73		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.73		Position offset: 25

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201201843; hg19: chr19-39907506;