Variant 3-75937491-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001378191.1(ROBO2):c.-3G>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00228 in 1,551,644 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

ROBO2
NM_001378191.1 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.49

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 Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 3-75937491-G-T is Benign according to our data. Variant chr3-75937491-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3035762.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 209 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
ROBO2	NM_001128929.3 linkuse as main transcript	c.-3G>T	5_prime_UTR_variant	2/27	NP_001122401.1
ROBO2	NM_001378190.1 linkuse as main transcript	c.-3G>T	5_prime_UTR_variant	2/29	NP_001365119.1
ROBO2	NM_001378191.1 linkuse as main transcript	c.-3G>T	5_prime_UTR_variant	2/30	NP_001365120.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
ROBO2	ENST00000471893.2 linkuse as main transcript	c.-3G>T	5_prime_UTR_variant	2/29	4	ENSP00000418190
ROBO2	ENST00000487694.7 linkuse as main transcript	c.-3G>T	5_prime_UTR_variant	2/27	5	ENSP00000417335	Q9HCK4-3
ROBO2	ENST00000602589.5 linkuse as main transcript	c.-3G>T	5_prime_UTR_variant	2/23	5	ENSP00000473268

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000783

AC:

179

AN:

228530

Hom.:

AF XY:

0.000847

AC XY:

107

AN XY:

126266

show subpopulations

Gnomad AFR exome

AF:

0.000215

Gnomad AMR exome

AF:

0.0000589

Gnomad ASJ exome

AF:

0.000203

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000663

Gnomad FIN exome

AF:

0.00147

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

AF:

0.00238

AC:

3333

AN:

1399492

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1662

AN XY:

693894

show subpopulations

Gnomad4 AFR exome

AF:

0.000398

Gnomad4 AMR exome

AF:

0.000101

Gnomad4 ASJ exome

AF:

0.000200

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000241

Gnomad4 FIN exome

AF:

0.00371

Gnomad4 NFE exome

AF:

0.00279

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152152

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00108

EpiCase

AF:

0.00164

EpiControl

AF:

0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ROBO2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 27, 2019

This variant is classified as likely 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_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.81

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