NM_004560.4:c.97+65166A>G

Variant names:

• chr9-91884701-T-C
• rs10761134
• NM_004560.4:c.97+65166A>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.97+65166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,860 control chromosomes in the GnomAD database, including 17,277 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 0.44 (17277 hom., cov: 31)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 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+65166A>G		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.97+65166A>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.97+65166A>G		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-324+63906A>G		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.97+65166A>G		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66305 AN: 151744 Hom.: 17237 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.437 AC: 66388 AN: 151860 Hom.: 17277 Cov.: 31 AF XY: 0.441 AC XY: 32700 AN XY: 74216

African (AFR) AF: 0.722 AC: 29876 AN: 41394

American (AMR) AF: 0.517 AC: 7881 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.453 AC: 2332 AN: 5152

South Asian (SAS) AF: 0.340 AC: 1634 AN: 4804

European-Finnish (FIN) AF: 0.323 AC: 3399 AN: 10532

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19102 AN: 67938

Other (OTH) AF: 0.403 AC: 851 AN: 2114

Alfa AF: 0.337 Hom.: 5287

Bravo AF: 0.465

Asia WGS AF: 0.426 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.37
PhyloP100		0.0040
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: rs10761134; hg19: chr9-94646983;