NM_001394212.1:c.130+114517G>C

Variant names:

• chr3-76425934-G-C
• rs9827843
• NM_001394212.1:c.130+114517G>C

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+114517G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,010 control chromosomes in the GnomAD database, including 34,484 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 0.67 (34484 hom., cov: 32)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+114517G>C		intron_variant	Intron 1 of 27		NP_001381141.1
ROBO2	NM_001378191.1	c.109+488332G>C		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378192.1	c.130+114517G>C		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.109+488332G>C		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.109+488332G>C		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.109+488332G>C		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101177 AN: 151892 Hom.: 34435 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.666 AC: 101287 AN: 152010 Hom.: 34484 Cov.: 32 AF XY: 0.668 AC XY: 49614 AN XY: 74284

African (AFR) AF: 0.817 AC: 33928 AN: 41514

American (AMR) AF: 0.692 AC: 10558 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3468

East Asian (EAS) AF: 0.576 AC: 2963 AN: 5146

South Asian (SAS) AF: 0.632 AC: 3041 AN: 4808

European-Finnish (FIN) AF: 0.657 AC: 6929 AN: 10554

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39719 AN: 67934

Other (OTH) AF: 0.648 AC: 1368 AN: 2112

Alfa AF: 0.468 Hom.: 1164

Bravo AF: 0.676

Asia WGS AF: 0.608 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.072
DANN	Benign	0.42
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs9827843; hg19: chr3-76475085;