rs10992075

Variant names:

• chr9-91739609-A-G
• rs10992075
• NM_004560.4:c.495-2091T>C

Variant summary

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

The NM_004560.4(ROR2):​c.495-2091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,870 control chromosomes in the GnomAD database, including 7,707 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 0.31 (7707 hom., cov: 31)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 5 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), PanelApp Australia
• autosomal recessive Robinow syndrome

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004560.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	NM_004560.4	MANE Select	c.495-2091T>C		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.495-2091T>C		intron	N/A	NP_001305133.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	ENST00000375708.4	TSL:1 MANE Select	c.495-2091T>C		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.75-2091T>C		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.495-2091T>C		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47289 AN: 151752 Hom.: 7691 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.324

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.312 AC: 47342 AN: 151870 Hom.: 7707 Cov.: 31 AF XY: 0.313 AC XY: 23210 AN XY: 74226

African (AFR) AF: 0.393 AC: 16254 AN: 41394

American (AMR) AF: 0.323 AC: 4931 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1637 AN: 5172

South Asian (SAS) AF: 0.248 AC: 1192 AN: 4810

European-Finnish (FIN) AF: 0.319 AC: 3349 AN: 10502

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18123 AN: 67954

Other (OTH) AF: 0.305 AC: 642 AN: 2104

Alfa AF: 0.282 Hom.: 10691

Bravo AF: 0.322

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.011
DANN	Benign	0.46
PhyloP100		-3.1
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: rs10992075; hg19: chr9-94501891;