NM_001394212.1:c.130+333181G>A

Variant names:

• chr3-76644598-G-A
• rs6764287
• NM_001394212.1:c.130+333181G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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, PanelApp Australia, 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394212.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	NM_001394212.1		c.130+333181G>A		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.110-453416G>A		intron	N/A	NP_001365120.1	A0A8Q3SIW8
	ROBO2	NM_001378192.1		c.130+333181G>A		intron	N/A	NP_001365121.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.110-453416G>A		intron	N/A	ENSP00000512767.1	A0A8Q3SIW8
	ROBO2	ENST00000696629.1		c.110-453416G>A		intron	N/A	ENSP00000512766.1	A0A8Q3SIU0
	ROBO2	ENST00000471893.2	TSL:4	c.110-453416G>A		intron	N/A	ENSP00000418190.2	H7C4U9

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

African (AFR) AF: 0.625 AC: 25870 AN: 41420

American (AMR) AF: 0.553 AC: 8441 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2122 AN: 3464

East Asian (EAS) AF: 0.490 AC: 2517 AN: 5134

South Asian (SAS) AF: 0.551 AC: 2651 AN: 4814

European-Finnish (FIN) AF: 0.683 AC: 7222 AN: 10570

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 43010 AN: 67956

Other (OTH) AF: 0.590 AC: 1247 AN: 2112

Alfa AF: 0.623 Hom.: 116233

Bravo AF: 0.607

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.67
PhyloP100		-0.36

Splicing

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

Other links and lift over

dbSNP: rs6764287; hg19: chr3-76693749;