rs7863557

Positions:

chr9-91775833-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004560.4(ROR2):c.98-15G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,610,440 control chromosomes in the GnomAD database, including 50,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4175 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46432 hom. )

Consequence

ROR2
NM_004560.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0310

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-91775833-C-G is Benign according to our data. Variant chr9-91775833-C-G is described in ClinVar as [Benign]. Clinvar id is 159823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-91775833-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR2	NM_004560.4 linkuse as main transcript	c.98-15G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375708.4 linkuse as main transcript	c.98-15G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004560.4	P1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34611

AN:

151976

Hom.:

4164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.0624

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.221

AC:

55302

AN:

250208

Hom.:

6886

AF XY:

0.228

AC XY:

30863

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.0612

Gnomad SAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.246

AC:

359414

AN:

1458346

Hom.:

46432

Cov.:

AF XY:

0.248

AC XY:

180225

AN XY:

725660

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.302

Gnomad4 EAS exome

AF:

0.0382

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.228

AC:

34656

AN:

152094

Hom.:

4175

Cov.:

AF XY:

0.223

AC XY:

16545

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.306

Gnomad4 EAS

AF:

0.0624

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.256

Hom.:

930

Bravo

AF:

0.225

Asia WGS

AF:

0.193

AC:

673

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

Autosomal recessive Robinow syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Brachydactyly type B1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.0

DANN

Benign

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over