3-77436987-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO2	NM_001395656.1	c.389-40427C>T		intron_variant		ENST00000696593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO2	ENST00000696593.1	c.389-40427C>T		intron_variant			NM_001395656.1	A2

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

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.264

Alfa AF: 0.340 Hom.: 9524

Bravo AF: 0.261

Asia WGS AF: 0.231 AC: 806 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.26
Dann	Benign	0.35

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: rs12634690; hg19: chr3-77486138;