dbSNP rs13064369: ROBO2:c.668-3177C>T (chr3-77490067-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001395656.1(ROBO2):c.668-3177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 150,664 control chromosomes in the GnomAD database, including 20,879 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 20879 hom., cov: 28)

Consequence

ROBO2
NM_001395656.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

4 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
familial vesicoureteral reflux
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ROBO2 links:

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new If you want to explore the variant's impact on the transcript NM_001395656.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395656.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROBO2	NM_001395656.1	MANE Select	c.668-3177C>T	intron	N/A	NP_001382585.1	A0A8Q3WLE3
ROBO2	NM_001394212.1		c.737-3177C>T	intron	N/A	NP_001381141.1
ROBO2	NM_001378191.1		c.716-3177C>T	intron	N/A	NP_001365120.1	A0A8Q3SIW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROBO2	ENST00000696593.1	MANE Select	c.668-3177C>T	intron	N/A	ENSP00000512738.1	A0A8Q3WLE3
ROBO2	ENST00000461745.5	TSL:1	c.668-3177C>T	intron	N/A	ENSP00000417164.1	Q9HCK4-1
ROBO2	ENST00000473767.5	TSL:1	n.668-3177C>T	intron	N/A	ENSP00000418117.1	F8WBR3

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

78640

AN:

150562

Hom.:

20861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.631

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.537

Gnomad OTH

AF:

0.556

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.522

AC:

78690

AN:

150664

Hom.:

20879

Cov.:

AF XY:

0.525

AC XY:

38597

AN XY:

73480

show subpopulations

African (AFR)

AF:

0.427

AC:

17476

AN:

40948

American (AMR)

AF:

0.632

AC:

9563

AN:

15138

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

2044

AN:

3468

East Asian (EAS)

AF:

0.589

AC:

3000

AN:

5096

South Asian (SAS)

AF:

0.571

AC:

2726

AN:

4776

European-Finnish (FIN)

AF:

0.568

AC:

5781

AN:

10186

Middle Eastern (MID)

AF:

0.517

AC:

150

AN:

290

European-Non Finnish (NFE)

AF:

0.537

AC:

36403

AN:

67760

Other (OTH)

AF:

0.559

AC:

1171

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1860

3719

5579

7438

9298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.542

Hom.:

16779

Bravo

AF:

0.525

Asia WGS

AF:

0.608

AC:

2114

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.48

(source)

DANN

Benign

0.74

PhyloP100

-1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over