Genetic Variant ROR2:c.97+62889T>A (chr9-91886978-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004560.4(ROR2):c.97+62889T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,938 control chromosomes in the GnomAD database, including 33,000 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 0.64 ( 32996 hom., cov: 31)

Exomes 𝑓: 0.64 ( 4 hom. )

Consequence

ROR2
NM_004560.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

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

ROR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 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+62889T>A		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.97+62889T>A		intron	N/A	NP_001305133.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROR2	ENST00000375708.4	TSL:1 MANE Select	c.97+62889T>A	intron	N/A	ENSP00000364860.3	Q01974
ROR2	ENST00000375715.5	TSL:1	c.-324+61629T>A	intron	N/A	ENSP00000364867.1	B1APY4
ROR2	ENST00000964760.1		c.97+62889T>A	intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96810

AN:

151798

Hom.:

32939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.609

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.609

GnomAD4 exome

AF:

0.636

AC:

AN:

Hom.:

Cov.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.638

AC:

96922

AN:

151916

Hom.:

32996

Cov.:

AF XY:

0.640

AC XY:

47451

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.887

AC:

36781

AN:

41476

American (AMR)

AF:

0.663

AC:

10117

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1817

AN:

3466

East Asian (EAS)

AF:

0.609

AC:

3112

AN:

5110

South Asian (SAS)

AF:

0.562

AC:

2710

AN:

4820

European-Finnish (FIN)

AF:

0.556

AC:

5854

AN:

10530

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.509

AC:

34597

AN:

67940

Other (OTH)

AF:

0.610

AC:

1288

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1575

3150

4725

6300

7875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.590

Hom.:

3476

Bravo

AF:

0.656

Asia WGS

AF:

0.628

AC:

2188

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

0.59

(source)

DANN

Benign

0.71

PhyloP100

-1.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over