rs264537

chr3-76673615-C-Gchr3-76673615-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO2	NM_001128929.3	c.110-424399C>G		intron_variant
ROBO2	NM_001378190.1	c.110-424399C>G		intron_variant
ROBO2	NM_001378191.1	c.110-424399C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO2	ENST00000471893.2	c.110-424399C>G		intron_variant		4
ROBO2	ENST00000475334.2	c.130+362198C>G		intron_variant		5		A1
ROBO2	ENST00000487694.7	c.110-424399C>G		intron_variant		5

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

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.434

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.61
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs264537; hg19: chr3-76722766;