rs264537

Variant names:

• chr3-76673615-C-G
• rs264537
• NM_001394212.1:c.130+362198C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-76673615-C-G
• chr3-76673615-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394212.1(ROBO2):​c.130+362198C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,856 control chromosomes in the GnomAD database, including 16,459 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 (16459 hom., cov: 32)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	NM_001394212.1		c.130+362198C>G		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.110-424399C>G		intron	N/A	NP_001365120.1
	ROBO2	NM_001378192.1		c.130+362198C>G		intron	N/A	NP_001365121.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.110-424399C>G		intron	N/A	ENSP00000512767.1
	ROBO2	ENST00000696629.1		c.110-424399C>G		intron	N/A	ENSP00000512766.1
	ROBO2	ENST00000471893.2	TSL:4	c.110-424399C>G		intron	N/A	ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69767 AN: 151738 Hom.: 16438 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.460 AC: 69844 AN: 151856 Hom.: 16459 Cov.: 32 AF XY: 0.459 AC XY: 34083 AN XY: 74198

African (AFR) AF: 0.546 AC: 22597 AN: 41398

American (AMR) AF: 0.430 AC: 6553 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1970 AN: 5168

South Asian (SAS) AF: 0.532 AC: 2551 AN: 4792

European-Finnish (FIN) AF: 0.459 AC: 4832 AN: 10516

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28840 AN: 67948

Other (OTH) AF: 0.434 AC: 914 AN: 2108

Alfa AF: 0.319 Hom.: 841

Bravo AF: 0.460

Asia WGS AF: 0.459 AC: 1594 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	0.61
DANN	Benign	0.32
PhyloP100		-0.099

Splicing

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

Other links and lift over

dbSNP: rs264537; hg19: chr3-76722766;