Variant 3-75937512-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 10/14 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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. Variant chr3-75937512-C-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
ROBO2	NM_001378191.1 linkuse as main transcript	c.19C>A	p.Arg7Ser	missense_variant	2/30	NP_001365120.1
ROBO2	NM_001378190.1 linkuse as main transcript	c.19C>A	p.Arg7Ser	missense_variant	2/29	NP_001365119.1
ROBO2	NM_001378195.1 linkuse as main transcript	c.19C>A	p.Arg7Ser	missense_variant	2/29	NP_001365124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein
ROBO2	ENST00000696630.1 linkuse as main transcript	c.19C>A	p.Arg7Ser	missense_variant	2/30		ENSP00000512767
ROBO2	ENST00000696629.1 linkuse as main transcript	c.19C>A	p.Arg7Ser	missense_variant	2/29		ENSP00000512766
ROBO2	ENST00000471893.2 linkuse as main transcript	c.19C>A	p.Arg7Ser	missense_variant	2/29	4	ENSP00000418190

Frequencies

GnomAD3 genomes

Cov.:

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

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:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Feb 15, 2016	- -

ROBO2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 2020

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

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

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over