chr3-77040382-G-A

Variant names:

• chr3-77040382-G-A
• rs79942150
• NM_001395656.1:c.-404G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395656.1(ROBO2):​c.-404G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000467 in 856,606 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: 0.0000047 (0 hom.)
• Consequence: ROBO2 NM_001395656.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.-404G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 28	ENST00000696593.1	NP_001382585.1
ROBO2	NM_001395656.1	c.-404G>A		5_prime_UTR_variant	Exon 1 of 28	ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593	c.-404G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 28		NM_001395656.1	ENSP00000512738.1
ROBO2	ENST00000696593	c.-404G>A		5_prime_UTR_variant	Exon 1 of 28		NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000467 AC: 4 AN: 856606 Hom.: 0 Cov.: 33 AF XY: 0.00000504 AC XY: 2 AN XY: 396744

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000514

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	-0.32
CADD	Benign	20
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79942150; hg19: chr3-77089533;