rs4639579

Variant names:

• chr9-91833073-A-C
• rs4639579
• NM_004560.4:c.98-57255T>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.98-57255T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,072 control chromosomes in the GnomAD database, including 4,923 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 0.24 (4923 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.409 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.98-57255T>G		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.98-57255T>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.98-57255T>G		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-323-57255T>G		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.98-57255T>G		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36730 AN: 151956 Hom.: 4916 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.242 AC: 36748 AN: 152072 Hom.: 4923 Cov.: 32 AF XY: 0.249 AC XY: 18496 AN XY: 74316

African (AFR) AF: 0.172 AC: 7143 AN: 41530

American (AMR) AF: 0.417 AC: 6373 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1820 AN: 5142

South Asian (SAS) AF: 0.233 AC: 1121 AN: 4814

European-Finnish (FIN) AF: 0.293 AC: 3097 AN: 10586

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15700 AN: 67942

Other (OTH) AF: 0.251 AC: 530 AN: 2108

Alfa AF: 0.231 Hom.: 716

Bravo AF: 0.251

Asia WGS AF: 0.291 AC: 1011 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	0.15
DANN	Benign	0.66
PhyloP100		-1.2
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: rs4639579; hg19: chr9-94595355;