chr3-76481689-A-G

Variant names:

• chr3-76481689-A-G
• rs11915977
• NM_001394212.1:c.130+170272A>G

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+170272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,084 control chromosomes in the GnomAD database, including 842 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 0.10 (842 hom., cov: 32)
• Consequence: ROBO2 NM_001394212.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001394212.1	c.130+170272A>G		intron_variant	Intron 1 of 27		NP_001381141.1
ROBO2	NM_001378191.1	c.109+544087A>G		intron_variant	Intron 2 of 29		NP_001365120.1
ROBO2	NM_001378192.1	c.130+170272A>G		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+544087A>G		intron_variant	Intron 2 of 29			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.109+544087A>G		intron_variant	Intron 2 of 28			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.109+544087A>G		intron_variant	Intron 2 of 28	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15266 AN: 151966 Hom.: 840 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.00406

Gnomad SAS AF: 0.0552

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.100 AC: 15281 AN: 152084 Hom.: 842 Cov.: 32 AF XY: 0.0983 AC XY: 7312 AN XY: 74354

African (AFR) AF: 0.109 AC: 4523 AN: 41508

American (AMR) AF: 0.0827 AC: 1261 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3468

East Asian (EAS) AF: 0.00407 AC: 21 AN: 5158

South Asian (SAS) AF: 0.0548 AC: 264 AN: 4818

European-Finnish (FIN) AF: 0.121 AC: 1285 AN: 10590

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7324 AN: 67986

Other (OTH) AF: 0.119 AC: 251 AN: 2106

Alfa AF: 0.0992 Hom.: 399

Bravo AF: 0.0989

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.25
DANN	Benign	0.75
PhyloP100		-0.95

Splicing

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

Other links and lift over

dbSNP: rs11915977; hg19: chr3-76530840;