chr3-76632821-A-T

Variant names:

• chr3-76632821-A-T
• rs2044580
• NM_001394212.1:c.130+321404A>T

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+321404A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,120 control chromosomes in the GnomAD database, including 30,173 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 0.63 (30173 hom., cov: 33)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+321404A>T		intron_variant	Intron 1 of 27		NP_001381141.1
ROBO2	NM_001378191.1	c.110-465193A>T		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378192.1	c.130+321404A>T		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.110-465193A>T		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.110-465193A>T		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.110-465193A>T		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95309 AN: 152002 Hom.: 30133 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.627 AC: 95413 AN: 152120 Hom.: 30173 Cov.: 33 AF XY: 0.626 AC XY: 46572 AN XY: 74376

African (AFR) AF: 0.684 AC: 28413 AN: 41510

American (AMR) AF: 0.574 AC: 8769 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3470

East Asian (EAS) AF: 0.696 AC: 3604 AN: 5180

South Asian (SAS) AF: 0.538 AC: 2598 AN: 4826

European-Finnish (FIN) AF: 0.665 AC: 7048 AN: 10600

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41111 AN: 67950

Other (OTH) AF: 0.603 AC: 1272 AN: 2108

Alfa AF: 0.623 Hom.: 3681

Bravo AF: 0.626

Asia WGS AF: 0.584 AC: 2028 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.040

Splicing

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

Other links and lift over

dbSNP: rs2044580; hg19: chr3-76681972;