rs12171318

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001378191.1(ROBO2):c.19C>A(p.Arg7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ROBO2
NM_001378191.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.539

Publications

2 publications found

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]

ROBO2 Gene-Disease associations (from GenCC):

vesicoureteral reflux 2
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial vesicoureteral reflux
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ROBO2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0021585822).

BP6

Variant 3-75937512-C-A is Benign according to our data. Variant chr3-75937512-C-A is described in ClinVar as [Benign]. Clinvar id is 518348.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
ROBO2	NM_001378191.1 link	c.19C>A	p.Arg7Ser	missense_variant	Exon 2 of 30	NP_001365120.1
ROBO2	NM_001378190.1 link	c.19C>A	p.Arg7Ser	missense_variant	Exon 2 of 29	NP_001365119.1
ROBO2	NM_001378195.1 link	c.19C>A	p.Arg7Ser	missense_variant	Exon 2 of 29	NP_001365124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
ROBO2	ENST00000696630.1 link	c.19C>A	p.Arg7Ser	missense_variant	Exon 2 of 30		ENSP00000512767.1	A0A8Q3SIW8
ROBO2	ENST00000696629.1 link	c.19C>A	p.Arg7Ser	missense_variant	Exon 2 of 29		ENSP00000512766.1	A0A8Q3SIU0
ROBO2	ENST00000471893.2 link	c.19C>A	p.Arg7Ser	missense_variant	Exon 2 of 29	4	ENSP00000418190.2	H7C4U9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.500

AC:

113387

AN:

226762

AF XY:

0.500

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.500

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.500

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1419592

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704832

African (AFR)

AF:

0.00

AC:

AN:

33096

American (AMR)

AF:

0.00

AC:

AN:

42136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25526

East Asian (EAS)

AF:

0.00

AC:

AN:

39070

South Asian (SAS)

AF:

0.00

AC:

AN:

81422

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096662

Other (OTH)

AF:

0.00

AC:

AN:

59206

GnomAD4 genome

Cov.:

Alfa

AF:

0.242

Hom.:

ExAC

AF:

0.497

AC:

57339

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Vesicoureteral reflux 2

Benign:2

Feb 15, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

ROBO2-related disorder

Benign:1

Nov 18, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.24

(source)

DANN

Benign

0.57

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-1.0

PhyloP100

0.54

PROVEAN

Benign

0.43

N;.

REVEL

Benign

0.014

Sift

Benign

0.93

T;.

Sift4G

Benign

0.48

T;T

Vest4

0.064

MPC

0.25

ClinPred

0.0038

GERP RS

0.34

gMVP

0.73

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over