3-77270336-A-G

Variant names:

• chr3-77270336-A-G
• rs17015112
• NM_001395656.1:c.388+171996A>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.388+171996A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,212 control chromosomes in the GnomAD database, including 3,045 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 0.17 (3045 hom., cov: 33)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.388+171996A>G		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+171996A>G		intron_variant	Intron 2 of 27		NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26326 AN: 152094 Hom.: 3034 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.173 AC: 26368 AN: 152212 Hom.: 3045 Cov.: 33 AF XY: 0.180 AC XY: 13364 AN XY: 74432

African (AFR) AF: 0.188 AC: 7822 AN: 41540

American (AMR) AF: 0.241 AC: 3681 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3278 AN: 5160

South Asian (SAS) AF: 0.148 AC: 716 AN: 4826

European-Finnish (FIN) AF: 0.183 AC: 1941 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8051 AN: 68010

Other (OTH) AF: 0.170 AC: 358 AN: 2110

Alfa AF: 0.141 Hom.: 6028

Bravo AF: 0.181

Asia WGS AF: 0.326 AC: 1130 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.016
DANN	Benign	0.60
PhyloP100		-1.8

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: rs17015112; hg19: chr3-77319487;