chr9-91756046-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004560.4(ROR2):c.494+25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,609,944 control chromosomes in the GnomAD database, including 413,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35975 hom., cov: 33)

Exomes 𝑓: 0.72 ( 377446 hom. )

Consequence

ROR2
NM_004560.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.451

Publications

13 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 9-91756046-C-T is Benign according to our data. Variant chr9-91756046-C-T is described in ClinVar as Benign. ClinVar VariationId is 259431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4 link	c.494+25G>A		intron_variant	Intron 4 of 8	ENST00000375708.4	NP_004551.2	Q01974

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ROR2	ENST00000375708.4 link	c.494+25G>A	intron_variant	Intron 4 of 8	1	NM_004560.4	ENSP00000364860.3	Q01974
ROR2	ENST00000375715.5 link	c.74+25G>A	intron_variant	Intron 4 of 12	1		ENSP00000364867.1	B1APY4
ROR2	ENST00000548585.2 link	n.228G>A	non_coding_transcript_exon_variant	Exon 3 of 3	5
ROR2	ENST00000550066.5 link	n.962+25G>A	intron_variant	Intron 6 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

104039

AN:

152030

Hom.:

35952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.641

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.699

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.658

GnomAD2 exomes

AF:

0.669

AC:

168073

AN:

251288

AF XY:

0.678

show subpopulations

Gnomad AFR exome

AF:

0.633

Gnomad AMR exome

AF:

0.513

Gnomad ASJ exome

AF:

0.692

Gnomad EAS exome

AF:

0.468

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.734

Gnomad OTH exome

AF:

0.693

GnomAD4 exome

AF:

0.717

AC:

1044840

AN:

1457796

Hom.:

377446

Cov.:

AF XY:

0.718

AC XY:

520797

AN XY:

725564

show subpopulations

African (AFR)

AF:

0.637

AC:

21236

AN:

33354

American (AMR)

AF:

0.530

AC:

23682

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

18094

AN:

26110

East Asian (EAS)

AF:

0.467

AC:

18527

AN:

39680

South Asian (SAS)

AF:

0.706

AC:

60817

AN:

86180

European-Finnish (FIN)

AF:

0.699

AC:

37334

AN:

53408

Middle Eastern (MID)

AF:

0.712

AC:

4104

AN:

5764

European-Non Finnish (NFE)

AF:

0.738

AC:

818496

AN:

1108346

Other (OTH)

AF:

0.706

AC:

42550

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

13650

27301

40951

54602

68252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19936

39872

59808

79744

99680

<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:

0.684

AC:

104107

AN:

152148

Hom.:

35975

Cov.:

AF XY:

0.680

AC XY:

50559

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.641

AC:

26592

AN:

41474

American (AMR)

AF:

0.612

AC:

9355

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

2381

AN:

3470

East Asian (EAS)

AF:

0.481

AC:

2488

AN:

5176

South Asian (SAS)

AF:

0.698

AC:

3363

AN:

4816

European-Finnish (FIN)

AF:

0.705

AC:

7460

AN:

10586

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.739

AC:

50258

AN:

68018

Other (OTH)

AF:

0.654

AC:

1378

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1675

3349

5024

6698

8373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.720

Hom.:

10424

Bravo

AF:

0.671

Asia WGS

AF:

0.577

AC:

2007

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 16, 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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive Robinow syndrome

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Brachydactyly type B1

Benign:1

Nov 07, 2021

Genome-Nilou Lab

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

-0.88

CADD

Benign

0.66

(source)

DANN

Benign

0.80

PhyloP100

-0.45

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

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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