chr3-76676752-G-A

Variant names:

• chr3-76676752-G-A
• rs10511052
• NM_001394212.1:c.130+365335G>A

Variant summary

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

The NM_001394212.1(ROBO2):​c.130+365335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,042 control chromosomes in the GnomAD database, including 1,642 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 (1642 hom., cov: 31)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+365335G>A		intron_variant	Intron 1 of 27		NP_001381141.1
ROBO2	NM_001378191.1	c.110-421262G>A		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378192.1	c.130+365335G>A		intron_variant	Intron 1 of 27		NP_001365121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696630.1	c.110-421262G>A		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.110-421262G>A		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.110-421262G>A		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16688 AN: 151924 Hom.: 1629 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0451

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.110 AC: 16744 AN: 152042 Hom.: 1642 Cov.: 31 AF XY: 0.109 AC XY: 8093 AN XY: 74334

African (AFR) AF: 0.258 AC: 10704 AN: 41422

American (AMR) AF: 0.0827 AC: 1264 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3466

East Asian (EAS) AF: 0.144 AC: 743 AN: 5148

South Asian (SAS) AF: 0.159 AC: 767 AN: 4822

European-Finnish (FIN) AF: 0.0451 AC: 478 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0365 AC: 2483 AN: 67992

Other (OTH) AF: 0.0927 AC: 196 AN: 2114

Alfa AF: 0.0653 Hom.: 1718

Bravo AF: 0.119

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.56
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs10511052; hg19: chr3-76725903;