3-75937544-G-T

Variant names:

• chr3-75937544-G-T
• rs79015247
• NM_001378191.1:c.51G>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001378191.1(ROBO2):​c.51G>T​(p.Pro17Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000421 in 1,425,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: ROBO2 NM_001378191.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001378191.1	c.51G>T	p.Pro17Pro	synonymous_variant	Exon 2 of 30		NP_001365120.1
ROBO2	NM_001378190.1	c.51G>T	p.Pro17Pro	synonymous_variant	Exon 2 of 29		NP_001365119.1
ROBO2	NM_001378195.1	c.51G>T	p.Pro17Pro	synonymous_variant	Exon 2 of 29		NP_001365124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696630.1	c.51G>T	p.Pro17Pro	synonymous_variant	Exon 2 of 30			ENSP00000512767.1
ROBO2	ENST00000696629.1	c.51G>T	p.Pro17Pro	synonymous_variant	Exon 2 of 29			ENSP00000512766.1
ROBO2	ENST00000471893.2	c.51G>T	p.Pro17Pro	synonymous_variant	Exon 2 of 29	4		ENSP00000418190.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000421 AC: 6 AN: 1425306 Hom.: 0 Cov.: 30 AF XY: 0.00000706 AC XY: 5 AN XY: 707942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000365

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.09e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.028
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs79015247; hg19: chr3-75986695;