chr3-76227391-G-C

Variant names:

• chr3-76227391-G-C
• rs10511040
• NM_001378191.1:c.109+289789G>C

Variant summary

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

The NM_001378191.1(ROBO2):​c.109+289789G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,080 control chromosomes in the GnomAD database, including 1,386 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 0.11 (1386 hom., cov: 33)
• Consequence: ROBO2 NM_001378191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001378191.1	c.109+289789G>C		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378190.1	c.109+289789G>C		intron_variant	Intron 2 of 28		NP_001365119.1
ROBO2	NM_001378195.1	c.109+289789G>C		intron_variant	Intron 2 of 28		NP_001365124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696630.1	c.109+289789G>C		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.109+289789G>C		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.109+289789G>C		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17122 AN: 151962 Hom.: 1381 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.113 AC: 17149 AN: 152080 Hom.: 1386 Cov.: 33 AF XY: 0.115 AC XY: 8525 AN XY: 74346

African (AFR) AF: 0.193 AC: 8007 AN: 41476

American (AMR) AF: 0.178 AC: 2728 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1355 AN: 5152

South Asian (SAS) AF: 0.107 AC: 515 AN: 4824

European-Finnish (FIN) AF: 0.0510 AC: 540 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0498 AC: 3386 AN: 67964

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.0804 Hom.: 108

Bravo AF: 0.131

Asia WGS AF: 0.202 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.49
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs10511040; hg19: chr3-76276542;