chr3-76672262-T-G

Variant names:

• chr3-76672262-T-G
• rs1349008
• NM_001394212.1:c.130+360845T>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+360845T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,650 control chromosomes in the GnomAD database, including 9,066 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 0.33 (9066 hom., cov: 30)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 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+360845T>G		intron	N/A	NP_001381141.1
	ROBO2	NM_001378191.1		c.110-425752T>G		intron	N/A	NP_001365120.1
	ROBO2	NM_001378192.1		c.130+360845T>G		intron	N/A	NP_001365121.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.110-425752T>G		intron	N/A	ENSP00000512767.1
	ROBO2	ENST00000696629.1		c.110-425752T>G		intron	N/A	ENSP00000512766.1
	ROBO2	ENST00000471893.2	TSL:4	c.110-425752T>G		intron	N/A	ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49898 AN: 151530 Hom.: 9075 Cov.: 30

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.329 AC: 49891 AN: 151650 Hom.: 9066 Cov.: 30 AF XY: 0.329 AC XY: 24405 AN XY: 74114

African (AFR) AF: 0.167 AC: 6926 AN: 41388

American (AMR) AF: 0.406 AC: 6163 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1484 AN: 3464

East Asian (EAS) AF: 0.527 AC: 2695 AN: 5116

South Asian (SAS) AF: 0.385 AC: 1852 AN: 4806

European-Finnish (FIN) AF: 0.317 AC: 3328 AN: 10502

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.384 AC: 26106 AN: 67898

Other (OTH) AF: 0.361 AC: 755 AN: 2094

Alfa AF: 0.370 Hom.: 32875

Bravo AF: 0.329

Asia WGS AF: 0.431 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.47
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs1349008; hg19: chr3-76721413;