3-77436987-C-T

Variant names:

• chr3-77436987-C-T
• rs12634690
• NM_001395656.1:c.389-40427C>T

Variant summary

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

The NM_001395656.1(ROBO2):​c.389-40427C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,824 control chromosomes in the GnomAD database, including 6,652 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 0.28 (6652 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• 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, 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	NM_001395656.1	MANE Select	c.389-40427C>T		intron	N/A	NP_001382585.1	A0A8Q3WLE3
	ROBO2	NM_001394212.1		c.458-40427C>T		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.437-40427C>T		intron	N/A	NP_001365120.1	A0A8Q3SIW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696593.1	MANE Select	c.389-40427C>T		intron	N/A	ENSP00000512738.1	A0A8Q3WLE3
	ROBO2	ENST00000461745.5	TSL:1	c.389-40427C>T		intron	N/A	ENSP00000417164.1	Q9HCK4-1
	ROBO2	ENST00000473767.5	TSL:1	n.389-40427C>T		intron	N/A	ENSP00000418117.1	F8WBR3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42479 AN: 151706 Hom.: 6657 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.280 AC: 42472 AN: 151824 Hom.: 6652 Cov.: 32 AF XY: 0.276 AC XY: 20498 AN XY: 74196

African (AFR) AF: 0.156 AC: 6463 AN: 41494

American (AMR) AF: 0.210 AC: 3204 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1506 AN: 3462

East Asian (EAS) AF: 0.260 AC: 1342 AN: 5164

South Asian (SAS) AF: 0.289 AC: 1393 AN: 4816

European-Finnish (FIN) AF: 0.351 AC: 3708 AN: 10576

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 23965 AN: 67782

Other (OTH) AF: 0.264 AC: 554 AN: 2100

Alfa AF: 0.337 Hom.: 10970

Bravo AF: 0.261

Asia WGS AF: 0.231 AC: 806 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.35
PhyloP100		-0.80

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: rs12634690; hg19: chr3-77486138;