rs11790808

Variant names:

• chr9-91826216-T-C
• rs11790808
• NM_004560.4:c.98-50398A>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.98-50398A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 152,248 control chromosomes in the GnomAD database, including 152 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 0.037 (152 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 7 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

ENSG00000299518 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0884 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.98-50398A>G		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.98-50398A>G		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.98-50398A>G		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-323-50398A>G		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.98-50398A>G		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.0370 AC: 5633 AN: 152130 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0480

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0370 AC: 5630 AN: 152248 Hom.: 152 Cov.: 32 AF XY: 0.0363 AC XY: 2702 AN XY: 74434

African (AFR) AF: 0.0100 AC: 416 AN: 41554

American (AMR) AF: 0.0333 AC: 510 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3470

East Asian (EAS) AF: 0.0953 AC: 492 AN: 5162

South Asian (SAS) AF: 0.0612 AC: 295 AN: 4822

European-Finnish (FIN) AF: 0.0321 AC: 341 AN: 10610

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0480 AC: 3266 AN: 68018

Other (OTH) AF: 0.0440 AC: 93 AN: 2112

Alfa AF: 0.0459 Hom.: 292

Bravo AF: 0.0354

Asia WGS AF: 0.0780 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.034
DANN	Benign	0.45
PhyloP100		-1.8
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: rs11790808; hg19: chr9-94588498;