3-76421322-A-G

Variant names:

• chr3-76421322-A-G
• rs6796472
• NM_001394212.1:c.130+109905A>G

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+109905A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,114 control chromosomes in the GnomAD database, including 10,709 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 0.29 (10709 hom., cov: 32)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• 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, 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	NM_001394212.1		c.130+109905A>G		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.109+483720A>G		intron	N/A	NP_001365120.1
	ROBO2	NM_001378192.1		c.130+109905A>G		intron	N/A	NP_001365121.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.109+483720A>G		intron	N/A	ENSP00000512767.1
	ROBO2	ENST00000696629.1		c.109+483720A>G		intron	N/A	ENSP00000512766.1
	ROBO2	ENST00000471893.2	TSL:4	c.109+483720A>G		intron	N/A	ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44090 AN: 151996 Hom.: 10678 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.290 AC: 44175 AN: 152114 Hom.: 10709 Cov.: 32 AF XY: 0.286 AC XY: 21288 AN XY: 74370

African (AFR) AF: 0.661 AC: 27378 AN: 41442

American (AMR) AF: 0.280 AC: 4275 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1659 AN: 5170

South Asian (SAS) AF: 0.114 AC: 549 AN: 4832

European-Finnish (FIN) AF: 0.121 AC: 1278 AN: 10604

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.115 AC: 7816 AN: 68006

Other (OTH) AF: 0.277 AC: 585 AN: 2112

Alfa AF: 0.163 Hom.: 6418

Bravo AF: 0.324

Asia WGS AF: 0.268 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.33
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs6796472; hg19: chr3-76470473;