3-76279082-A-G

Variant names:

• chr3-76279082-A-G
• rs992323
• NM_001378191.1:c.109+341480A>G

Variant summary

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

The NM_001378191.1(ROBO2):​c.109+341480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 151,114 control chromosomes in the GnomAD database, including 40,456 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 0.69 (40456 hom., cov: 30)
• Consequence: ROBO2 NM_001378191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378191.1. 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_001378191.1		c.109+341480A>G		intron	N/A	NP_001365120.1
	ROBO2	NM_001378190.1		c.109+341480A>G		intron	N/A	NP_001365119.1
	ROBO2	NM_001378195.1		c.109+341480A>G		intron	N/A	NP_001365124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.109+341480A>G		intron	N/A	ENSP00000512767.1
	ROBO2	ENST00000696629.1		c.109+341480A>G		intron	N/A	ENSP00000512766.1
	ROBO2	ENST00000471893.2	TSL:4	c.109+341480A>G		intron	N/A	ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 104481 AN: 151028 Hom.: 40466 Cov.: 30

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.691 AC: 104477 AN: 151114 Hom.: 40456 Cov.: 30 AF XY: 0.690 AC XY: 50895 AN XY: 73786

African (AFR) AF: 0.351 AC: 14474 AN: 41244

American (AMR) AF: 0.584 AC: 8805 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3052 AN: 3466

East Asian (EAS) AF: 0.534 AC: 2746 AN: 5140

South Asian (SAS) AF: 0.786 AC: 3767 AN: 4794

European-Finnish (FIN) AF: 0.889 AC: 9230 AN: 10380

Middle Eastern (MID) AF: 0.755 AC: 219 AN: 290

European-Non Finnish (NFE) AF: 0.885 AC: 59974 AN: 67738

Other (OTH) AF: 0.679 AC: 1415 AN: 2084

Alfa AF: 0.781 Hom.: 5906

Bravo AF: 0.646

Asia WGS AF: 0.629 AC: 2180 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.89
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs992323; hg19: chr3-76328233; COSMIC: COSV72215242;