rs10992063

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004560.4(ROR2):c.2088C>T(p.Tyr696=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,613,784 control chromosomes in the GnomAD database, including 154,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14708 hom., cov: 33)

Exomes 𝑓: 0.43 ( 139525 hom. )

Consequence

ROR2
NM_004560.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.45

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 9-91724406-G-A is Benign according to our data. Variant chr9-91724406-G-A is described in ClinVar as [Benign]. Clinvar id is 159815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-91724406-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.489 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.2088C>T	p.Tyr696=	synonymous_variant	9/9	ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ROR2	ENST00000375708.4 linkuse as main transcript	c.2088C>T	p.Tyr696=	synonymous_variant	9/9	1	NM_004560.4	P1
ROR2	ENST00000375715.5 linkuse as main transcript	c.1668C>T	p.Tyr556=	synonymous_variant	9/13	1
ROR2	ENST00000550066.5 linkuse as main transcript	n.2556C>T		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66573

AN:

151922

Hom.:

14710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.435

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.417

GnomAD3 exomes

AF:

0.433

AC:

108721

AN:

251002

Hom.:

24292

AF XY:

0.422

AC XY:

57284

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.557

Gnomad ASJ exome

AF:

0.379

Gnomad EAS exome

AF:

0.401

Gnomad SAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.435

Gnomad OTH exome

AF:

0.420

GnomAD4 exome

AF:

0.434

AC:

634653

AN:

1461744

Hom.:

139525

Cov.:

AF XY:

0.429

AC XY:

312248

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.436

Gnomad4 AMR exome

AF:

0.555

Gnomad4 ASJ exome

AF:

0.378

Gnomad4 EAS exome

AF:

0.445

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.440

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.438

AC:

66585

AN:

152040

Hom.:

14708

Cov.:

AF XY:

0.437

AC XY:

32495

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.435

Gnomad4 AMR

AF:

0.499

Gnomad4 ASJ

AF:

0.379

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.440

Gnomad4 OTH

AF:

0.413

Alfa

AF:

0.436

Hom.:

8475

Bravo

AF:

0.444

Asia WGS

AF:

0.347

AC:

1205

AN:

3478

EpiCase

AF:

0.425

EpiControl

AF:

0.415

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 14, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

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

Autosomal recessive Robinow syndrome

Benign:1

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. -

Brachydactyly type B1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

Cadd

Benign

3.4

Dann

Benign

0.54

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