Genetic Variant ROBO2:c.130+123615T>C (chr3-76435032-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001394212.1(ROBO2):c.130+123615T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,343,278 control chromosomes in the GnomAD database, including 180,139 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 0.46 ( 16932 hom., cov: 32)

Exomes 𝑓: 0.52 ( 163207 hom. )

Consequence

ROBO2
NM_001394212.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

7 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 links:

CAP1P1 (HGNC:31134): (CAP1 pseudogene 1)

CAP1P1 links:

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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=-0.56).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394212.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
ROBO2	NM_001394212.1	c.130+123615T>C	intron	N/A	NP_001381141.1
ROBO2	NM_001378191.1	c.109+497430T>C	intron	N/A	NP_001365120.1
ROBO2	NM_001378192.1	c.130+123615T>C	intron	N/A	NP_001365121.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ROBO2	ENST00000696630.1		c.109+497430T>C	intron	N/A	ENSP00000512767.1
ROBO2	ENST00000696629.1		c.109+497430T>C	intron	N/A	ENSP00000512766.1
ROBO2	ENST00000471893.2	TSL:4	c.109+497430T>C	intron	N/A	ENSP00000418190.2

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70160

AN:

151866

Hom.:

16925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.578

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.462

GnomAD4 exome

AF:

0.520

AC:

619603

AN:

1191294

Hom.:

163207

Cov.:

AF XY:

0.523

AC XY:

316977

AN XY:

606056

show subpopulations

African (AFR)

AF:

0.312

AC:

8721

AN:

27984

American (AMR)

AF:

0.519

AC:

22927

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.568

AC:

13793

AN:

24278

East Asian (EAS)

AF:

0.440

AC:

16879

AN:

38358

South Asian (SAS)

AF:

0.594

AC:

47858

AN:

80632

European-Finnish (FIN)

AF:

0.566

AC:

30045

AN:

53066

Middle Eastern (MID)

AF:

0.501

AC:

2619

AN:

5226

European-Non Finnish (NFE)

AF:

0.520

AC:

450868

AN:

866222

Other (OTH)

AF:

0.504

AC:

25893

AN:

51348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

16845

33689

50534

67378

84223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11552

23104

34656

46208

57760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.462

AC:

70200

AN:

151984

Hom.:

16932

Cov.:

AF XY:

0.467

AC XY:

34670

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.321

AC:

13289

AN:

41442

American (AMR)

AF:

0.445

AC:

6792

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

2003

AN:

3466

East Asian (EAS)

AF:

0.466

AC:

2401

AN:

5152

South Asian (SAS)

AF:

0.594

AC:

2856

AN:

4810

European-Finnish (FIN)

AF:

0.570

AC:

6015

AN:

10558

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.518

AC:

35228

AN:

67974

Other (OTH)

AF:

0.460

AC:

970

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1896

3791

5687

7582

9478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.492

Hom.:

39864

Bravo

AF:

0.445

Asia WGS

AF:

0.468

AC:

1629

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

(source)

DANN

Benign

0.86

PhyloP100

1.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over