3-75937512-C-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_001378191.1(ROBO2):c.19C>A(p.Arg7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ROBO2
NM_001378191.1 missense
NM_001378191.1 missense
Scores
13
Clinical Significance
Conservation
PhyloP100: 0.539
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0021585822).
BP6
?
Variant 3-75937512-C-A is Benign according to our data. Variant chr3-75937512-C-A is described in ClinVar as [Benign]. Clinvar id is 518348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-75937512-C-A is described in Lovd as [Benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROBO2 | NM_001378191.1 | c.19C>A | p.Arg7Ser | missense_variant | 2/30 | ||
ROBO2 | NM_001378190.1 | c.19C>A | p.Arg7Ser | missense_variant | 2/29 | ||
ROBO2 | NM_001378195.1 | c.19C>A | p.Arg7Ser | missense_variant | 2/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROBO2 | ENST00000696630.1 | c.19C>A | p.Arg7Ser | missense_variant | 2/30 | ||||
ROBO2 | ENST00000696629.1 | c.19C>A | p.Arg7Ser | missense_variant | 2/29 | ||||
ROBO2 | ENST00000471893.2 | c.19C>A | p.Arg7Ser | missense_variant | 2/29 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1419592Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 704832
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1419592
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
704832
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
ExAC
?
AF:
AC:
57339
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Vesicoureteral reflux 2 Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Feb 15, 2016 | - - |
ROBO2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 18, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Vest4
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at