3-77040961-C-T

Position:

• chr3-77040961-C-T

Variant summary

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

The NM_001395656.1(ROBO2):​c.61+115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,392,942 control chromosomes in the GnomAD database, including 5,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (330 hom., cov: 32)
  • Exomes 𝑓: 0.083 (4841 hom.)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0350

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=-0.82).
• BP6: Variant 3-77040961-C-T is Benign according to our data. Variant chr3-77040961-C-T is described in ClinVar as [Benign]. Clinvar id is 1247361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROBO2	NM_001395656.1	c.61+115C>T		intron_variant		ENST00000696593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROBO2	ENST00000696593.1	c.61+115C>T		intron_variant			NM_001395656.1	A2

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8602 AN: 149006 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0299

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.00160

Gnomad SAS AF: 0.0378

Gnomad FIN AF: 0.0621

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.0568

GnomAD4 exome AF: 0.0826 AC: 102765 AN: 1243832 Hom.: 4841 AF XY: 0.0819 AC XY: 51380 AN XY: 627470

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.0275

Gnomad4 ASJ exome AF: 0.0619

Gnomad4 EAS exome AF: 0.000208

Gnomad4 SAS exome AF: 0.0474

Gnomad4 FIN exome AF: 0.0689

Gnomad4 NFE exome AF: 0.0958

Gnomad4 OTH exome AF: 0.0717

GnomAD4 genome AF: 0.0577 AC: 8599 AN: 149110 Hom.: 330 Cov.: 32 AF XY: 0.0548 AC XY: 3975 AN XY: 72586

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.00161

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0621

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.0562

Alfa AF: 0.0777 Hom.: 121

Bravo AF: 0.0529

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.61

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: rs114060047; hg19: chr3-77090112;