9-91818976-T-C

Variant names:

• chr9-91818976-T-C
• rs4743855
• NM_004560.4:c.98-43158A>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.98-43158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,002 control chromosomes in the GnomAD database, including 26,044 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 0.54 (26044 hom., cov: 31)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• 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), 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 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.98-43158A>G		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.98-43158A>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.98-43158A>G		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-323-43158A>G		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.98-43158A>G		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82583 AN: 151884 Hom.: 25983 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.544 AC: 82701 AN: 152002 Hom.: 26044 Cov.: 31 AF XY: 0.545 AC XY: 40460 AN XY: 74264

African (AFR) AF: 0.879 AC: 36482 AN: 41512

American (AMR) AF: 0.530 AC: 8096 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1319 AN: 3468

East Asian (EAS) AF: 0.622 AC: 3205 AN: 5150

South Asian (SAS) AF: 0.436 AC: 2090 AN: 4798

European-Finnish (FIN) AF: 0.417 AC: 4404 AN: 10550

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25448 AN: 67938

Other (OTH) AF: 0.507 AC: 1071 AN: 2114

Alfa AF: 0.427 Hom.: 28881

Bravo AF: 0.569

Asia WGS AF: 0.560 AC: 1948 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	0.33
DANN	Benign	0.71
PhyloP100		-1.4
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: rs4743855; hg19: chr9-94581258;