rs7037255

Variant names:

• chr9-91934672-G-A
• rs7037255
• NM_004560.4:c.97+15195C>T

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+15195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,976 control chromosomes in the GnomAD database, including 23,272 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 0.52 (23272 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 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+15195C>T		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.97+15195C>T		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+15195C>T		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-324+13935C>T		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.97+15195C>T		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79186 AN: 151860 Hom.: 23220 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.522 AC: 79297 AN: 151976 Hom.: 23272 Cov.: 32 AF XY: 0.523 AC XY: 38810 AN XY: 74254

African (AFR) AF: 0.800 AC: 33210 AN: 41488

American (AMR) AF: 0.561 AC: 8576 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1609 AN: 3468

East Asian (EAS) AF: 0.503 AC: 2596 AN: 5156

South Asian (SAS) AF: 0.450 AC: 2164 AN: 4810

European-Finnish (FIN) AF: 0.378 AC: 3975 AN: 10518

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25653 AN: 67946

Other (OTH) AF: 0.490 AC: 1031 AN: 2106

Alfa AF: 0.429 Hom.: 18619

Bravo AF: 0.546

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.17
PhyloP100		-0.0050
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: rs7037255; hg19: chr9-94696954;