rs13064369

chr3-77490067-C-T

Variant summary

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

The NM_001395656.1(ROBO2):c.668-3177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 150,664 control chromosomes in the GnomAD database, including 20,879 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 0.52 (20879 hom., cov: 28)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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 (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO2	NM_001395656.1	c.668-3177C>T		intron_variant		ENST00000696593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO2	ENST00000696593.1	c.668-3177C>T		intron_variant			NM_001395656.1	A2

Frequencies

GnomAD3 genomes AF: 0.522 AC: 78640 AN: 150562 Hom.: 20861 Cov.: 28

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.522 AC: 78690 AN: 150664 Hom.: 20879 Cov.: 28 AF XY: 0.525 AC XY: 38597 AN XY: 73480

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.559

Alfa AF: 0.544 Hom.: 12532

Bravo AF: 0.525

Asia WGS AF: 0.608 AC: 2114 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	0.48
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs13064369; hg19: chr3-77539218;