chr3-77560504-C-A

Variant names:

• chr3-77560504-C-A
• rs1403848
• NM_001395656.1:c.1450-2147C>A

Variant summary

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

The NM_001395656.1(ROBO2):​c.1450-2147C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,912 control chromosomes in the GnomAD database, including 28,643 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 0.61 (28643 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.1450-2147C>A		intron_variant	Intron 10 of 27	ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593.1	c.1450-2147C>A		intron_variant	Intron 10 of 27		NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92479 AN: 151794 Hom.: 28616 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.609 AC: 92560 AN: 151912 Hom.: 28643 Cov.: 32 AF XY: 0.610 AC XY: 45244 AN XY: 74230

African (AFR) AF: 0.705 AC: 29212 AN: 41460

American (AMR) AF: 0.645 AC: 9836 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2300 AN: 3472

East Asian (EAS) AF: 0.654 AC: 3362 AN: 5142

South Asian (SAS) AF: 0.612 AC: 2952 AN: 4820

European-Finnish (FIN) AF: 0.499 AC: 5251 AN: 10532

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37575 AN: 67922

Other (OTH) AF: 0.640 AC: 1350 AN: 2108

Alfa AF: 0.595 Hom.: 20720

Bravo AF: 0.625

Asia WGS AF: 0.661 AC: 2298 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		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

Other links and lift over

dbSNP: rs1403848; hg19: chr3-77609655;