3-77337984-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395656.1(ROBO2):c.389-139430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,148 control chromosomes in the GnomAD database, including 2,340 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 0.16 (2340 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO2	NM_001395656.1	c.389-139430A>G		intron_variant		ENST00000696593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO2	ENST00000696593.1	c.389-139430A>G		intron_variant			NM_001395656.1	A2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24808 AN: 152030 Hom.: 2344 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.163 AC: 24803 AN: 152148 Hom.: 2340 Cov.: 32 AF XY: 0.164 AC XY: 12161 AN XY: 74376

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.163

Alfa AF: 0.195 Hom.: 1458

Bravo AF: 0.156

Asia WGS AF: 0.161 AC: 560 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.6
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10511055; hg19: chr3-77387135;