3-75937491-G-A

Variant names:

• chr3-75937491-G-A
• rs769883087
• NM_001378191.1:c.-3G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378191.1(ROBO2):​c.-3G>A variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ROBO2 NM_001378191.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49
• 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, 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001378191.1	c.-3G>A		5_prime_UTR_variant	Exon 2 of 30		NP_001365120.1
ROBO2	NM_001378190.1	c.-3G>A		5_prime_UTR_variant	Exon 2 of 29		NP_001365119.1
ROBO2	NM_001378195.1	c.-3G>A		5_prime_UTR_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.-3G>A		5_prime_UTR_variant	Exon 2 of 30			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.-3G>A		5_prime_UTR_variant	Exon 2 of 29			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.-3G>A		5_prime_UTR_variant	Exon 2 of 29	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 228530 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000143 AC: 2 AN: 1399506 Hom.: 0 Cov.: 28 AF XY: 0.00000144 AC XY: 1 AN XY: 693904

African (AFR) AF: 0.00 AC: 0 AN: 32698

American (AMR) AF: 0.00 AC: 0 AN: 39800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25032

East Asian (EAS) AF: 0.00 AC: 0 AN: 38554

South Asian (SAS) AF: 0.00 AC: 0 AN: 78716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5266

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1084916

Other (OTH) AF: 0.00 AC: 0 AN: 58450

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		4.5

Splicing

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

Other links and lift over

dbSNP: rs769883087; hg19: chr3-75986642;