3-77515159-C-G

Variant names:

• chr3-77515159-C-G
• rs9309770
• NM_001395656.1:c.807-7616C>G

Variant summary

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

The NM_001395656.1(ROBO2):​c.807-7616C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 151,670 control chromosomes in the GnomAD database, including 49,898 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 0.80 (49898 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.807-7616C>G		intron_variant	Intron 5 of 27	ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593.1	c.807-7616C>G		intron_variant	Intron 5 of 27		NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 121812 AN: 151552 Hom.: 49839 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.804 AC: 121931 AN: 151670 Hom.: 49898 Cov.: 32 AF XY: 0.809 AC XY: 59947 AN XY: 74138

African (AFR) AF: 0.938 AC: 38924 AN: 41480

American (AMR) AF: 0.846 AC: 12854 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2847 AN: 3462

East Asian (EAS) AF: 0.961 AC: 4921 AN: 5120

South Asian (SAS) AF: 0.813 AC: 3921 AN: 4822

European-Finnish (FIN) AF: 0.765 AC: 8095 AN: 10586

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47813 AN: 67712

Other (OTH) AF: 0.826 AC: 1735 AN: 2100

Alfa AF: 0.648 Hom.: 1794

Bravo AF: 0.818

Asia WGS AF: 0.894 AC: 3111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.65
PhyloP100		-0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9309770; hg19: chr3-77564310;