rs754279676

Variant summary

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

The NM_001395656.1(ROBO2):​c.95G>A​(p.Arg32Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,408 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ROBO2
NM_001395656.1 missense

Scores

3
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 10.0
Variant links:
Genes affected
ROBO2 (HGNC:10250): (roundabout guidance receptor 2) The protein encoded by this gene belongs to the ROBO family, part of the immunoglobulin superfamily of proteins that are highly conserved from fly to human. The encoded protein is a transmembrane receptor for the slit homolog 2 protein and functions in axon guidance and cell migration. Mutations in this gene are associated with vesicoureteral reflux, characterized by the backward flow of urine from the bladder into the ureters or the kidney. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
ROBO2NM_001395656.1 linkuse as main transcriptc.95G>A p.Arg32Gln missense_variant 2/28 ENST00000696593.1 NP_001382585.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ROBO2ENST00000696593.1 linkuse as main transcriptc.95G>A p.Arg32Gln missense_variant 2/28 NM_001395656.1 ENSP00000512738 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1434408
Hom.:
0
Cov.:
31
AF XY:
0.00000282
AC XY:
2
AN XY:
708284
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:
0.00000183
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Pathogenic:1
Likely pathogenic, no assertion criteria providedresearchGharavi Laboratory, Columbia UniversitySep 16, 2018- -
Congenital anomaly of kidney and urinary tract Uncertain:1
Uncertain significance, criteria provided, single submittercurationInstitute of Human Genetics, University of Leipzig Medical CenterJan 09, 2021This ROBO2 variant was reported as Likely pathogenic​ in PMID: 30586318 with original nomenclature reported as p.R32Q. Variant was re-classified as Uncertain Significance based on the criteria PM1_Moderate, PM2_Supporting. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.38
.;.;T;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D;D
M_CAP
Benign
0.073
D
MetaRNN
Uncertain
0.73
D;D;D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Benign
1.2
.;.;L;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-2.8
D;.;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.024
D;.;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
1.0, 0.99
.;.;D;D
Vest4
0.82
MVP
0.78
MPC
0.26
ClinPred
0.95
D
GERP RS
5.1
Varity_R
0.50
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs754279676; hg19: chr3-77147198; COSMIC: COSV59922580; API