rs4744113

Variant names:

• chr9-91886649-C-T
• rs4744113
• NM_004560.4:c.97+63218G>A

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+63218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,156 control chromosomes in the GnomAD database, including 6,748 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 0.29 (6748 hom., cov: 33)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 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.97+63218G>A		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.97+63218G>A		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.97+63218G>A		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-324+61958G>A		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.97+63218G>A		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44044 AN: 152016 Hom.: 6737 Cov.: 33

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.136 AC: 3 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 2 AN: 16

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.290 AC: 44072 AN: 152134 Hom.: 6748 Cov.: 33 AF XY: 0.296 AC XY: 22021 AN XY: 74364

African (AFR) AF: 0.322 AC: 13367 AN: 41528

American (AMR) AF: 0.437 AC: 6685 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1971 AN: 5150

South Asian (SAS) AF: 0.258 AC: 1247 AN: 4826

European-Finnish (FIN) AF: 0.294 AC: 3112 AN: 10578

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

European-Non Finnish (NFE) AF: 0.237 AC: 16094 AN: 67982

Other (OTH) AF: 0.283 AC: 598 AN: 2116

Alfa AF: 0.264 Hom.: 686

Bravo AF: 0.303

Asia WGS AF: 0.320 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.78
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4744113; hg19: chr9-94648931;