NM_004560.4:c.175+2391T>C

Variant names:

• chr9-91773350-A-G
• rs7039620
• NM_004560.4:c.175+2391T>C

Variant summary

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

The NM_004560.4(ROR2):​c.175+2391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,430 control chromosomes in the GnomAD database, including 4,253 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 0.23 (4253 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 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.175+2391T>C		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.175+2391T>C		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.175+2391T>C		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-246+2391T>C		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.175+2391T>C		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34286 AN: 151314 Hom.: 4233 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0927

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.227 AC: 34346 AN: 151430 Hom.: 4253 Cov.: 32 AF XY: 0.229 AC XY: 16973 AN XY: 74024

African (AFR) AF: 0.294 AC: 12154 AN: 41272

American (AMR) AF: 0.319 AC: 4866 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3464

East Asian (EAS) AF: 0.262 AC: 1346 AN: 5128

South Asian (SAS) AF: 0.141 AC: 672 AN: 4780

European-Finnish (FIN) AF: 0.220 AC: 2307 AN: 10500

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11553 AN: 67764

Other (OTH) AF: 0.227 AC: 474 AN: 2086

Alfa AF: 0.143 Hom.: 399

Bravo AF: 0.239

Asia WGS AF: 0.228 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.40
PhyloP100		-0.90
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: rs7039620; hg19: chr9-94535632;