dbSNP rs775748: ROBO2:c.1071+847T>A (chr3-77547309-T-A) – 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.1071+847T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,922 control chromosomes in the GnomAD database, including 22,388 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 0.54 ( 22388 hom., cov: 32)

Consequence

ROBO2
NM_001395656.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00700

Publications

5 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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.573 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.1071+847T>A	intron	N/A	NP_001382585.1	A0A8Q3WLE3
ROBO2	NM_001394212.1		c.1128+847T>A	intron	N/A	NP_001381141.1
ROBO2	NM_001378191.1		c.1119+847T>A	intron	N/A	NP_001365120.1	A0A8Q3SIW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROBO2	ENST00000696593.1	MANE Select	c.1071+847T>A	intron	N/A	ENSP00000512738.1	A0A8Q3WLE3
ROBO2	ENST00000461745.5	TSL:1	c.1059+847T>A	intron	N/A	ENSP00000417164.1	Q9HCK4-1
ROBO2	ENST00000473767.5	TSL:1	n.1059+847T>A	intron	N/A	ENSP00000418117.1	F8WBR3

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82289

AN:

151806

Hom.:

22390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.582

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

GnomAD4 genome

AF:

0.542

AC:

82306

AN:

151922

Hom.:

22388

Cov.:

AF XY:

0.543

AC XY:

40331

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.521

AC:

21580

AN:

41458

American (AMR)

AF:

0.583

AC:

8883

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2345

AN:

3468

East Asian (EAS)

AF:

0.522

AC:

2672

AN:

5118

South Asian (SAS)

AF:

0.563

AC:

2711

AN:

4812

European-Finnish (FIN)

AF:

0.495

AC:

5232

AN:

10576

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.544

AC:

36944

AN:

67942

Other (OTH)

AF:

0.579

AC:

1221

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1936

3873

5809

7746

9682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.532

Hom.:

2695

Bravo

AF:

0.549

Asia WGS

AF:

0.534

AC:

1861

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.85

(source)

DANN

Benign

0.36

PhyloP100

0.0070

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