rs2230577

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004560.4(ROR2):c.2154C>T(p.Pro718Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 1,613,426 control chromosomes in the GnomAD database, including 4,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 422 hom., cov: 33)

Exomes 𝑓: 0.073 ( 4461 hom. )

Consequence

ROR2
NM_004560.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -6.34

Publications

11 publications found

Variant links:

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)
autosomal recessive Robinow syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ROR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-91724340-G-A is Benign according to our data. Variant chr9-91724340-G-A is described in ClinVar as Benign. ClinVar VariationId is 159816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4 link	c.2154C>T	p.Pro718Pro	synonymous_variant	Exon 9 of 9	ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ROR2	ENST00000375708.4 link	c.2154C>T	p.Pro718Pro	synonymous_variant	Exon 9 of 9	1	NM_004560.4	ENSP00000364860.3
ROR2	ENST00000375715.5 link	c.1734C>T	p.Pro578Pro	synonymous_variant	Exon 9 of 13	1		ENSP00000364867.1
ROR2	ENST00000550066.5 link	n.2622C>T		non_coding_transcript_exon_variant	Exon 11 of 11	2

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9398

AN:

152180

Hom.:

416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0938

Gnomad ASJ

AF:

0.0570

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.0766

GnomAD2 exomes

AF:

0.0855

AC:

21384

AN:

250022

AF XY:

0.0851

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.0549

Gnomad EAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0661

Gnomad OTH exome

AF:

0.0759

GnomAD4 exome

AF:

0.0729

AC:

106494

AN:

1461128

Hom.:

4461

Cov.:

AF XY:

0.0737

AC XY:

53571

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.0118

AC:

396

AN:

33480

American (AMR)

AF:

0.122

AC:

5452

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0559

AC:

1460

AN:

26136

East Asian (EAS)

AF:

0.141

AC:

5583

AN:

39698

South Asian (SAS)

AF:

0.107

AC:

9189

AN:

86258

European-Finnish (FIN)

AF:

0.102

AC:

5383

AN:

52670

Middle Eastern (MID)

AF:

0.0565

AC:

326

AN:

5768

European-Non Finnish (NFE)

AF:

0.0667

AC:

74176

AN:

1112008

Other (OTH)

AF:

0.0750

AC:

4529

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

6927

13854

20781

27708

34635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2864

5728

8592

11456

14320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0618

AC:

9415

AN:

152298

Hom.:

422

Cov.:

AF XY:

0.0654

AC XY:

4868

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0144

AC:

599

AN:

41570

American (AMR)

AF:

0.0939

AC:

1437

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0570

AC:

198

AN:

3472

East Asian (EAS)

AF:

0.144

AC:

747

AN:

5176

South Asian (SAS)

AF:

0.108

AC:

520

AN:

4832

European-Finnish (FIN)

AF:

0.109

AC:

1158

AN:

10614

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0664

AC:

4517

AN:

68008

Other (OTH)

AF:

0.0844

AC:

178

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

464

928

1393

1857

2321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0624

Hom.:

507

Bravo

AF:

0.0571

Asia WGS

AF:

0.139

AC:

481

AN:

3478

EpiCase

AF:

0.0642

EpiControl

AF:

0.0649

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 10, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Autosomal recessive Robinow syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Brachydactyly type B1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.034

(source)

DANN

Benign

0.60

PhyloP100

-6.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over