chr17-43027183-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005440.5(RND2):c.191G>T(p.Gly64Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000289 in 1,593,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
RND2
NM_005440.5 missense, splice_region
NM_005440.5 missense, splice_region
Scores
12
3
1
Splicing: ADA: 0.9961
2
Clinical Significance
Conservation
PhyloP100: 4.85
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]
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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, 0.956
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RND2 | NM_005440.5 | c.191G>T | p.Gly64Val | missense_variant, splice_region_variant | 3/5 | ENST00000587250.4 | |
RND2 | XM_011525316.2 | c.191G>T | p.Gly64Val | missense_variant, splice_region_variant | 3/6 | ||
RND2 | XM_011525317.3 | c.107G>T | p.Gly36Val | missense_variant, splice_region_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RND2 | ENST00000587250.4 | c.191G>T | p.Gly64Val | missense_variant, splice_region_variant | 3/5 | 1 | NM_005440.5 | P1 | |
RND2 | ENST00000710494.1 | n.119G>T | splice_region_variant, non_coding_transcript_exon_variant | 2/4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152112Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000167 AC: 4AN: 239652Hom.: 0 AF XY: 0.0000154 AC XY: 2AN XY: 129584
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GnomAD4 exome AF: 0.0000284 AC: 41AN: 1441684Hom.: 0 Cov.: 29 AF XY: 0.0000209 AC XY: 15AN XY: 716674
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 10, 2023 | The c.191G>T (p.G64V) alteration is located in exon 3 (coding exon 3) of the RND2 gene. This alteration results from a G to T substitution at nucleotide position 191, causing the glycine (G) at amino acid position 64 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at