rs10761130

Variant names:

• chr9-91787904-A-C
• rs10761130
• NM_004560.4:c.98-12086T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004560.4(ROR2):​c.98-12086T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,138 control chromosomes in the GnomAD database, including 19,666 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 0.47 (19666 hom., cov: 33)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 1 publications found

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]

ROR2 Gene-Disease associations (from GenCC):

• brachydactyly type B1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive Robinow syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.98-12086T>G		intron_variant	Intron 1 of 8	ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.98-12086T>G		intron_variant	Intron 1 of 8	1	NM_004560.4	ENSP00000364860.3

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71549 AN: 152020 Hom.: 19661 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.470 AC: 71550 AN: 152138 Hom.: 19666 Cov.: 33 AF XY: 0.471 AC XY: 35044 AN XY: 74358

African (AFR) AF: 0.186 AC: 7738 AN: 41532

American (AMR) AF: 0.479 AC: 7315 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1714 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1714 AN: 5180

South Asian (SAS) AF: 0.419 AC: 2014 AN: 4810

European-Finnish (FIN) AF: 0.660 AC: 6979 AN: 10582

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.623 AC: 42359 AN: 67964

Other (OTH) AF: 0.477 AC: 1007 AN: 2110

Alfa AF: 0.544 Hom.: 3062

Bravo AF: 0.447

Asia WGS AF: 0.362 AC: 1258 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	7.7
DANN	Benign	0.67
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10761130; hg19: chr9-94550186;