NM_001395656.1:c.389-139430A>G

Variant names:

• chr3-77337984-A-G
• rs10511055
• NM_001395656.1:c.389-139430A>G

Variant summary

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

The NM_001395656.1(ROBO2):​c.389-139430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,148 control chromosomes in the GnomAD database, including 2,340 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 0.16 (2340 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395656.1. 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_001395656.1	MANE Select	c.389-139430A>G		intron	N/A	NP_001382585.1
	ROBO2	NM_001394212.1		c.458-139430A>G		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.437-139430A>G		intron	N/A	NP_001365120.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696593.1	MANE Select	c.389-139430A>G		intron	N/A	ENSP00000512738.1
	ROBO2	ENST00000461745.5	TSL:1	c.389-139430A>G		intron	N/A	ENSP00000417164.1
	ROBO2	ENST00000473767.5	TSL:1	n.389-139430A>G		intron	N/A	ENSP00000418117.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24808 AN: 152030 Hom.: 2344 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.163 AC: 24803 AN: 152148 Hom.: 2340 Cov.: 32 AF XY: 0.164 AC XY: 12161 AN XY: 74376

African (AFR) AF: 0.0710 AC: 2949 AN: 41552

American (AMR) AF: 0.132 AC: 2014 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1364 AN: 5166

South Asian (SAS) AF: 0.133 AC: 641 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2146 AN: 10594

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14339 AN: 67972

Other (OTH) AF: 0.163 AC: 344 AN: 2112

Alfa AF: 0.196 Hom.: 1610

Bravo AF: 0.156

Asia WGS AF: 0.161 AC: 560 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.63
PhyloP100		0.73

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: rs10511055; hg19: chr3-77387135;