rs73114594

Variant names:

• chr3-77603591-G-A
• rs73114594
• NM_001395656.1:c.3148+1100G>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.3148+1100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,100 control chromosomes in the GnomAD database, including 929 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 0.097 (929 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• Publications: 2 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

ENSG00000305342 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.3148+1100G>A		intron_variant	Intron 21 of 27	ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593.1	c.3148+1100G>A		intron_variant	Intron 21 of 27		NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14727 AN: 151984 Hom.: 930 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0967 AC: 14715 AN: 152100 Hom.: 929 Cov.: 32 AF XY: 0.0969 AC XY: 7203 AN XY: 74344

African (AFR) AF: 0.0241 AC: 1001 AN: 41510

American (AMR) AF: 0.0890 AC: 1360 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3468

East Asian (EAS) AF: 0.105 AC: 545 AN: 5176

South Asian (SAS) AF: 0.135 AC: 653 AN: 4824

European-Finnish (FIN) AF: 0.0995 AC: 1051 AN: 10560

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9098 AN: 67960

Other (OTH) AF: 0.109 AC: 230 AN: 2114

Alfa AF: 0.0826 Hom.: 288

Bravo AF: 0.0916

Asia WGS AF: 0.134 AC: 466 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.46
PhyloP100		-0.74

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: rs73114594; hg19: chr3-77652742;