chr17-43028595-G-T

Variant names:

• chr17-43028595-G-T
• rs143507179
• NM_005440.5:c.599G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005440.5(RND2):​c.599G>T​(p.Arg200Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R200Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RND2 NM_005440.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.97
• Publications: 0 publications found

Genes affected

RND2 (HGNC:18315): (Rho family GTPase 2) This gene encodes a member of the Rho GTPase family, whose members play a key role in the regulation of actin cytoskeleton organization in response to extracellular growth factors. This particular family member has been implicated in the regulation of neuronal morphology and endosomal trafficking. The gene localizes to chromosome 17 and is the centromeric neighbor of the breast-ovarian cancer susceptibility gene BRCA1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RND2	NM_005440.5	MANE Select	c.599G>T	p.Arg200Leu	missense	Exon 5 of 5	NP_005431.1	P52198

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RND2	ENST00000587250.4	TSL:1 MANE Select	c.599G>T	p.Arg200Leu	missense	Exon 5 of 5	ENSP00000466680.1	P52198
	RND2	ENST00000916371.1		c.572G>T	p.Arg191Leu	missense	Exon 5 of 5	ENSP00000586430.1
	RND2	ENST00000710494.1		n.527G>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.7	L
PhyloP100		10
PrimateAI	Uncertain	0.74	T
Sift4G	Uncertain	0.056	T
Polyphen		1.0	D
Vest4		0.69
MutPred		0.34		Gain of helix (P = 0.0034)
MVP		0.91
MPC		1.1
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.19
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs143507179; hg19: chr17-41180612;