chr3-75937512-CGT-TCA

Variant names:

• chr3-75937512-CGT-TCA
• NM_001378191.1:c.19_21delCGTinsTCA
• ROBO2 p.Arg7Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001378191.1(ROBO2):​c.19_21delCGTinsTCA​(p.Arg7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ROBO2 NM_001378191.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 0 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378191.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	NM_001378191.1		c.19_21delCGTinsTCA	p.Arg7Ser	missense	N/A	NP_001365120.1	A0A8Q3SIW8
	ROBO2	NM_001378190.1		c.19_21delCGTinsTCA	p.Arg7Ser	missense	N/A	NP_001365119.1
	ROBO2	NM_001378195.1		c.19_21delCGTinsTCA	p.Arg7Ser	missense	N/A	NP_001365124.1	A0A8Q3SIU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.19_21delCGTinsTCA	p.Arg7Ser	missense	N/A	ENSP00000512767.1	A0A8Q3SIW8
	ROBO2	ENST00000696629.1		c.19_21delCGTinsTCA	p.Arg7Ser	missense	N/A	ENSP00000512766.1	A0A8Q3SIU0
	ROBO2	ENST00000471893.2	TSL:4	c.19_21delCGTinsTCA	p.Arg7Ser	missense	N/A	ENSP00000418190.2	H7C4U9

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-75986663;