17-43028595-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RND2	NM_005440.5	c.599G>T	p.Arg200Leu	missense_variant	Exon 5 of 5	ENST00000587250.4	NP_005431.1
RND2	XM_011525316.2	c.599G>T	p.Arg200Leu	missense_variant	Exon 5 of 6		XP_011523618.1
RND2	XM_011525317.3	c.515G>T	p.Arg172Leu	missense_variant	Exon 5 of 6		XP_011523619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RND2	ENST00000587250.4	c.599G>T	p.Arg200Leu	missense_variant	Exon 5 of 5	1	NM_005440.5	ENSP00000466680.1
RND2	ENST00000710494.1	n.527G>T		non_coding_transcript_exon_variant	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 v4.3

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs143507179; hg19: chr17-41180612;