chr3-75937491-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 3035762.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 209 AD gene.

Transcripts

RefSeq

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

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

GnomAD3 exomes AF: 0.000783 AC: 179 AN: 228530 Hom.: 0 AF XY: 0.000847 AC XY: 107 AN XY: 126266

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 SAS exome AF: 0.0000663

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

Gnomad4 AFR exome AF: 0.000398

Gnomad4 AMR exome AF: 0.000101

Gnomad4 ASJ exome AF: 0.000200

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000241

Gnomad4 FIN exome AF: 0.00371

Gnomad4 NFE exome AF: 0.00279

Gnomad4 OTH exome AF: 0.00214

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

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00253

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.00108

EpiCase AF: 0.00164

EpiControl AF: 0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ROBO2-related disorder Benign:1

Nov 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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	-0.44
CADD	Benign	18
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs769883087; hg19: chr3-75986642;