dbSNP rs763612742: RND2:p.Gly64Asp (chr17-43027183-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005440.5(RND2):c.191G>A(p.Gly64Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000694 in 1,441,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RND2
NM_005440.5 missense, splice_region

Scores

Splicing: ADA: 0.6054

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.85

Variant links:

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]

RND2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RND2	NM_005440.5 link	c.191G>A	p.Gly64Asp	missense_variant, splice_region_variant	Exon 3 of 5	ENST00000587250.4	NP_005431.1	P52198
RND2	XM_011525316.2 link	c.191G>A	p.Gly64Asp	missense_variant, splice_region_variant	Exon 3 of 6		XP_011523618.1
RND2	XM_011525317.3 link	c.107G>A	p.Gly36Asp	missense_variant, splice_region_variant	Exon 3 of 6		XP_011523619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RND2	ENST00000587250.4 link	c.191G>A	p.Gly64Asp	missense_variant, splice_region_variant	Exon 3 of 5	1	NM_005440.5	ENSP00000466680.1		P52198
RND2	ENST00000710494.1 link	n.119G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

239652

Hom.:

AF XY:

0.00000772

AC XY:

AN XY:

129584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441684

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.44

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.5

PrimateAI

Pathogenic

0.84

Sift4G

Pathogenic

0.0

Polyphen

0.54

Vest4

0.78

MutPred

0.85

Gain of helix (P = 0.062);

MVP

0.99

MPC

1.1

ClinPred

0.94

GERP RS

4.1

Varity_R

0.91

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.61

dbscSNV1_RF

Benign

0.47

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over