chr3-75937491-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_001378191.1(ROBO2):​c.-3G>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00228 in 1,551,644 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (7 hom.)
• Consequence: ROBO2 NM_001378191.1 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 3-75937491-G-T is Benign according to our data. Variant chr3-75937491-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3035762.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 209 AD gene.

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.-3G>T		5_prime_UTR	Exon 2 of 30	NP_001365120.1	A0A8Q3SIW8
	ROBO2	NM_001378190.1		c.-3G>T		5_prime_UTR	Exon 2 of 29	NP_001365119.1
	ROBO2	NM_001378195.1		c.-3G>T		5_prime_UTR	Exon 2 of 29	NP_001365124.1	A0A8Q3SIU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO2	ENST00000696630.1		c.-3G>T		5_prime_UTR	Exon 2 of 30	ENSP00000512767.1	A0A8Q3SIW8
	ROBO2	ENST00000696629.1		c.-3G>T		5_prime_UTR	Exon 2 of 29	ENSP00000512766.1	A0A8Q3SIU0
	ROBO2	ENST00000471893.2	TSL:4	c.-3G>T		5_prime_UTR	Exon 2 of 29	ENSP00000418190.2	H7C4U9

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 209 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00253

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000783 AC: 179 AN: 228530 AF XY: 0.000847

Gnomad AFR exome AF: 0.000215

Gnomad AMR exome AF: 0.0000589

Gnomad ASJ exome AF: 0.000203

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00147

Gnomad NFE exome AF: 0.00137

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.00238 AC: 3333 AN: 1399492 Hom.: 7 Cov.: 28 AF XY: 0.00240 AC XY: 1662 AN XY: 693894

African (AFR) AF: 0.000398 AC: 13 AN: 32698

American (AMR) AF: 0.000101 AC: 4 AN: 39800

Ashkenazi Jewish (ASJ) AF: 0.000200 AC: 5 AN: 25032

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

South Asian (SAS) AF: 0.000241 AC: 19 AN: 78716

European-Finnish (FIN) AF: 0.00371 AC: 134 AN: 36074

Middle Eastern (MID) AF: 0.000190 AC: 1 AN: 5266

European-Non Finnish (NFE) AF: 0.00279 AC: 3032 AN: 1084902

Other (OTH) AF: 0.00214 AC: 125 AN: 58450

GnomAD4 genome AF: 0.00137 AC: 209 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74376

African (AFR) AF: 0.000145 AC: 6 AN: 41520

American (AMR) AF: 0.000131 AC: 2 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00253 AC: 172 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.00108

EpiCase AF: 0.00164

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ROBO2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
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;