rs9835590

Variant names:

• chr3-77039944-C-G
• rs9835590
• ENST00000461745.5:c.-842C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000461745.5(ROBO2):​c.-842C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 238,946 control chromosomes in the GnomAD database, including 14,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10958 hom., cov: 33)
  • Exomes 𝑓: 0.27 (3295 hom.)
• Consequence: ROBO2 ENST00000461745.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.417
• Publications: 1 publications found

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, Labcorp Genetics (formerly Invitae)
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-77039944-C-G is Benign according to our data. Variant chr3-77039944-C-G is described in ClinVar as [Benign]. Clinvar id is 1251594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.-842C>G		upstream_gene_variant		ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593.1	c.-842C>G		upstream_gene_variant			NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55294 AN: 151920 Hom.: 10933 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.271 AC: 23573 AN: 86912 Hom.: 3295 Cov.: 4 AF XY: 0.270 AC XY: 11278 AN XY: 41836

African (AFR) AF: 0.524 AC: 798 AN: 1522

American (AMR) AF: 0.325 AC: 26 AN: 80

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 94 AN: 522

East Asian (EAS) AF: 0.423 AC: 159 AN: 376

South Asian (SAS) AF: 0.297 AC: 497 AN: 1674

European-Finnish (FIN) AF: 0.367 AC: 11 AN: 30

Middle Eastern (MID) AF: 0.211 AC: 46 AN: 218

European-Non Finnish (NFE) AF: 0.266 AC: 21187 AN: 79624

Other (OTH) AF: 0.263 AC: 755 AN: 2866

GnomAD4 genome AF: 0.364 AC: 55377 AN: 152034 Hom.: 10958 Cov.: 33 AF XY: 0.365 AC XY: 27100 AN XY: 74318

African (AFR) AF: 0.520 AC: 21558 AN: 41496

American (AMR) AF: 0.366 AC: 5598 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 675 AN: 3472

East Asian (EAS) AF: 0.396 AC: 2011 AN: 5084

South Asian (SAS) AF: 0.328 AC: 1584 AN: 4824

European-Finnish (FIN) AF: 0.279 AC: 2958 AN: 10584

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19753 AN: 67954

Other (OTH) AF: 0.342 AC: 722 AN: 2112

Alfa AF: 0.343 Hom.: 1154

Bravo AF: 0.374

Asia WGS AF: 0.392 AC: 1360 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.68
PhyloP100		-0.42
PromoterAI		0.0016	Neutral

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

Other links and lift over

dbSNP: rs9835590; hg19: chr3-77089095;