9-91712589-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375715.5(ROR2):c.2065+4718A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 152,174 control chromosomes in the GnomAD database, including 71,943 homozygotes. 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: 𝑓 0.97 (71943 hom., cov: 29)
• Consequence: ROR2 ENST00000375715.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

Genes affected

ROR2 (HGNC:10257): (receptor tyrosine kinase like orphan receptor 2) The protein encoded by this gene is a receptor protein tyrosine kinase and type I transmembrane protein that belongs to the ROR subfamily of cell surface receptors. The protein may be involved in the early formation of the chondrocytes and may be required for cartilage and growth plate development. Mutations in this gene can cause brachydactyly type B, a skeletal disorder characterized by hypoplasia/aplasia of distal phalanges and nails. In addition, mutations in this gene can cause the autosomal recessive form of Robinow syndrome, which is characterized by skeletal dysplasia with generalized limb bone shortening, segmental defects of the spine, brachydactyly, and a dysmorphic facial appearance. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375715.5	c.2065+4718A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147821 AN: 152056 Hom.: 71881 Cov.: 29

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.961

Gnomad OTH AF: 0.974

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.972 AC: 147942 AN: 152174 Hom.: 71943 Cov.: 29 AF XY: 0.971 AC XY: 72245 AN XY: 74390

Gnomad4 AFR AF: 0.993

Gnomad4 AMR AF: 0.982

Gnomad4 ASJ AF: 0.957

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.940

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.961

Gnomad4 OTH AF: 0.974

Alfa AF: 0.968 Hom.: 8998

Bravo AF: 0.976

Asia WGS AF: 0.981 AC: 3411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.4
Dann	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9299397; hg19: chr9-94474871;