Genetic Variant ROBO2:c.-404G>A (chr3-77040382-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395656.1(ROBO2):c.-404G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000467 in 856,606 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

ROBO2
NM_001395656.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21

Publications

2 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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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

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.-404G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 28	NP_001382585.1	A0A8Q3WLE3
ROBO2	NM_001395656.1	MANE Select	c.-404G>A	5_prime_UTR	Exon 1 of 28	NP_001382585.1	A0A8Q3WLE3
ROBO2	NM_001378193.1		c.-404G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 27	NP_001365122.1	H7C4J7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROBO2	ENST00000696593.1	MANE Select	c.-404G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 28	ENSP00000512738.1	A0A8Q3WLE3
ROBO2	ENST00000461745.5	TSL:1	c.-404G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000417164.1	Q9HCK4-1
ROBO2	ENST00000696593.1	MANE Select	c.-404G>A	5_prime_UTR	Exon 1 of 28	ENSP00000512738.1	A0A8Q3WLE3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000467

AC:

AN:

856606

Hom.:

Cov.:

AF XY:

0.00000504

AC XY:

AN XY:

396744

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16322

American (AMR)

AF:

0.00

AC:

AN:

2290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5766

East Asian (EAS)

AF:

0.00

AC:

AN:

4566

South Asian (SAS)

AF:

0.00

AC:

AN:

18290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1694

European-Non Finnish (NFE)

AF:

0.00000514

AC:

AN:

777882

Other (OTH)

AF:

0.00

AC:

AN:

28612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

3.2

PromoterAI

-0.076

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over