rs10511057

Variant names:

• chr3-77280241-T-C
• rs10511057
• NM_001395656.1:c.388+181901T>C

Variant summary

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

The NM_001395656.1(ROBO2):​c.388+181901T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 152,282 control chromosomes in the GnomAD database, including 224 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 0.051 (224 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.388+181901T>C		intron_variant	Intron 2 of 27	ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593.1	c.388+181901T>C		intron_variant	Intron 2 of 27		NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7772 AN: 152164 Hom.: 223 Cov.: 32

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0846

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.0753

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0512 AC: 7791 AN: 152282 Hom.: 224 Cov.: 32 AF XY: 0.0529 AC XY: 3939 AN XY: 74444

African (AFR) AF: 0.0701 AC: 2916 AN: 41574

American (AMR) AF: 0.0846 AC: 1293 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3468

East Asian (EAS) AF: 0.0618 AC: 320 AN: 5174

South Asian (SAS) AF: 0.0756 AC: 365 AN: 4830

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10618

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0328 AC: 2228 AN: 68008

Other (OTH) AF: 0.0558 AC: 118 AN: 2116

Alfa AF: 0.0404 Hom.: 242

Bravo AF: 0.0552

Asia WGS AF: 0.0900 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.30
PhyloP100		-0.36

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: rs10511057; hg19: chr3-77329392;