rs79015247

Variant names:

• chr3-75937544-G-A
• rs79015247
• NM_001378191.1:c.51G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-75937544-G-A
• chr3-75937544-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001378191.1(ROBO2):​c.51G>A​(p.Pro17Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,425,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: ROBO2 NM_001378191.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.34
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-75937544-G-A is Benign according to our data. Variant chr3-75937544-G-A is described in ClinVar as [Benign]. Clinvar id is 3059993.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001378191.1	c.51G>A	p.Pro17Pro	synonymous_variant	Exon 2 of 30		NP_001365120.1
ROBO2	NM_001378190.1	c.51G>A	p.Pro17Pro	synonymous_variant	Exon 2 of 29		NP_001365119.1
ROBO2	NM_001378195.1	c.51G>A	p.Pro17Pro	synonymous_variant	Exon 2 of 29		NP_001365124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696630.1	c.51G>A	p.Pro17Pro	synonymous_variant	Exon 2 of 30			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.51G>A	p.Pro17Pro	synonymous_variant	Exon 2 of 29			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.51G>A	p.Pro17Pro	synonymous_variant	Exon 2 of 29	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.234 AC: 26016 AN: 111062 AF XY: 0.236

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.254

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.00000491 AC: 7 AN: 1425304 Hom.: 0 Cov.: 30 AF XY: 0.00000706 AC XY: 5 AN XY: 707940

African (AFR) AF: 0.00 AC: 0 AN: 33172

American (AMR) AF: 0.00 AC: 0 AN: 42698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25648

East Asian (EAS) AF: 0.00 AC: 0 AN: 39238

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000455 AC: 5 AN: 1100030

Other (OTH) AF: 0.0000168 AC: 1 AN: 59452

GnomAD4 genome Cov.: 32

Alfa AF: 0.161 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ROBO2-related disorder Benign:1

Nov 18, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.20
DANN	Benign	0.54
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs79015247; hg19: chr3-75986695; COSMIC: COSV72212161;