3-77039944-C-G

Position:

• chr3-77039944-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000461745.5(ROBO2):​c.-842C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 238,946 control chromosomes in the GnomAD database, including 14,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10958 hom., cov: 33)
  • Exomes 𝑓: 0.27 (3295 hom.)
• Consequence: ROBO2 ENST00000461745.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.417

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-77039944-C-G is Benign according to our data. Variant chr3-77039944-C-G is described in ClinVar as [Benign]. Clinvar id is 1251594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO2	NM_001128929.3	c.110-58070C>G		intron_variant			NP_001122401.1
ROBO2	NM_001378190.1	c.110-58070C>G		intron_variant			NP_001365119.1
ROBO2	NM_001378191.1	c.110-58070C>G		intron_variant			NP_001365120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000461745.5	c.-842C>G		5_prime_UTR_variant	1/26	1		ENSP00000417164	P4
ROBO2	ENST00000471893.2	c.110-58070C>G		intron_variant		4		ENSP00000418190
ROBO2	ENST00000475334.2	c.131-58070C>G		intron_variant		5		ENSP00000418446	A1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55294 AN: 151920 Hom.: 10933 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.271 AC: 23573 AN: 86912 Hom.: 3295 Cov.: 4 AF XY: 0.270 AC XY: 11278 AN XY: 41836

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.423

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.364 AC: 55377 AN: 152034 Hom.: 10958 Cov.: 33 AF XY: 0.365 AC XY: 27100 AN XY: 74318

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.342

Alfa AF: 0.343 Hom.: 1154

Bravo AF: 0.374

Asia WGS AF: 0.392 AC: 1360 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9835590; hg19: chr3-77089095;