rs767372181

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_004560.4(ROR2):c.904C>T(p.Arg302Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,603,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R302R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ROR2
NM_004560.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:2

Conservation

PhyloP100: 1.76

Publications

3 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: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

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.904C>T	p.Arg302Cys	missense	Exon 6 of 9	NP_004551.2
	ROR2	NM_001318204.2		c.904C>T	p.Arg302Cys	missense	Exon 6 of 8	NP_001305133.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ROR2	ENST00000375708.4	TSL:1 MANE Select	c.904C>T	p.Arg302Cys	missense	Exon 6 of 9	ENSP00000364860.3
ROR2	ENST00000375715.5	TSL:1	c.484C>T	p.Arg162Cys	missense	Exon 6 of 13	ENSP00000364867.1
ROR2	ENST00000964760.1		c.856+48C>T		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000445

AC:

AN:

224482

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1451144

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

43156

Ashkenazi Jewish (ASJ)

AF:

0.000155

AC:

AN:

25876

East Asian (EAS)

AF:

0.00

AC:

AN:

39338

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84670

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108612

Other (OTH)

AF:

0.00

AC:

AN:

59952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive Robinow syndrome (1)

Brachydactyly type B1;C5399974:Autosomal recessive Robinow syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.094

MutationAssessor

Uncertain

2.4

PhyloP100

1.8

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.87

MutPred

0.50

Loss of MoRF binding (P = 0.0507)

MVP

0.92

MPC

0.81

ClinPred

0.99

GERP RS

3.5

Varity_R

0.44

gMVP

0.80

Mutation Taster

=4/96

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over