chr3-75937590-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP6

The NM_001378191.1(ROBO2):c.97G>T(p.Gly33*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ROBO2
NM_001378191.1 stop_gained

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 5.00

Publications

1 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 3-75937590-G-T is Benign according to our data. Variant chr3-75937590-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 224347.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
ROBO2	NM_001378191.1 link	c.97G>T	p.Gly33*	stop_gained	Exon 2 of 30	NP_001365120.1
ROBO2	NM_001378190.1 link	c.97G>T	p.Gly33*	stop_gained	Exon 2 of 29	NP_001365119.1
ROBO2	NM_001378195.1 link	c.97G>T	p.Gly33*	stop_gained	Exon 2 of 29	NP_001365124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
ROBO2	ENST00000696630.1 link	c.97G>T	p.Gly33*	stop_gained	Exon 2 of 30		ENSP00000512767.1	A0A8Q3SIW8
ROBO2	ENST00000696629.1 link	c.97G>T	p.Gly33*	stop_gained	Exon 2 of 29		ENSP00000512766.1	A0A8Q3SIU0
ROBO2	ENST00000471893.2 link	c.97G>T	p.Gly33*	stop_gained	Exon 2 of 29	4	ENSP00000418190.2	H7C4U9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0195

AC:

3534

AN:

181206

AF XY:

0.0197

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.0215

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.0000573

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0226

GnomAD4 exome

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

AF:

0.00

AC:

AN:

1403380

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695790

African (AFR)

AF:

0.00

AC:

AN:

32768

American (AMR)

AF:

0.00

AC:

AN:

40318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25100

East Asian (EAS)

AF:

0.00

AC:

AN:

38562

South Asian (SAS)

AF:

0.00

AC:

AN:

79448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086834

Other (OTH)

AF:

0.00

AC:

AN:

58540

GnomAD4 genome

Cov.:

Alfa

AF:

0.124

Hom.:

ExAC

AF:

0.0736

AC:

8607

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Vesicoureteral reflux 2

Uncertain:2

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Apr 17, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

not provided

Benign:1

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ROBO2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.57

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.82

PhyloP100

5.0

Vest4

0.50

GERP RS

4.5

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