rs6764287

Positions:

• chr3-76644598-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394212.1(ROBO2):​c.130+333181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,926 control chromosomes in the GnomAD database, including 29,145 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 0.62 (29145 hom., cov: 32)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+333181G>A		intron_variant			NP_001381141.1
ROBO2	NM_001378191.1	c.110-453416G>A		intron_variant			NP_001365120.1
ROBO2	NM_001378192.1	c.130+333181G>A		intron_variant			NP_001365121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696630.1	c.110-453416G>A		intron_variant				ENSP00000512767.1
ROBO2	ENST00000696629.1	c.110-453416G>A		intron_variant				ENSP00000512766.1
ROBO2	ENST00000471893.2	c.110-453416G>A		intron_variant		4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93565 AN: 151808 Hom.: 29109 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.617 AC: 93664 AN: 151926 Hom.: 29145 Cov.: 32 AF XY: 0.614 AC XY: 45622 AN XY: 74260

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.590

Alfa AF: 0.619 Hom.: 49547

Bravo AF: 0.607

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6764287; hg19: chr3-76693749;