rs1534533

Variant names:

• chr9-91883689-T-A
• rs1534533
• NM_004560.4:c.97+66178A>T

Variant summary

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

The NM_004560.4(ROR2):​c.97+66178A>T 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 151,944 control chromosomes in the GnomAD database, including 19,565 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 (19565 hom., cov: 31)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	NM_004560.4	MANE Select	c.97+66178A>T		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.97+66178A>T		intron	N/A	NP_001305133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	ENST00000375708.4	TSL:1 MANE Select	c.97+66178A>T		intron	N/A	ENSP00000364860.3
	ROR2	ENST00000375715.5	TSL:1	c.-324+64918A>T		intron	N/A	ENSP00000364867.1
	ROR2	ENST00000495386.5	TSL:3	n.235-306A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71234 AN: 151826 Hom.: 19516 Cov.: 31

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.470 AC: 71338 AN: 151944 Hom.: 19565 Cov.: 31 AF XY: 0.472 AC XY: 35066 AN XY: 74252

African (AFR) AF: 0.754 AC: 31259 AN: 41450

American (AMR) AF: 0.543 AC: 8291 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1130 AN: 3466

East Asian (EAS) AF: 0.556 AC: 2869 AN: 5162

South Asian (SAS) AF: 0.374 AC: 1802 AN: 4818

European-Finnish (FIN) AF: 0.334 AC: 3516 AN: 10538

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21149 AN: 67936

Other (OTH) AF: 0.440 AC: 927 AN: 2108

Alfa AF: 0.414 Hom.: 1669

Bravo AF: 0.499

Asia WGS AF: 0.496 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.48
PhyloP100		-0.68
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: rs1534533; hg19: chr9-94645971; COSMIC: COSV107484856;