9-91722646-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004560.4(ROR2):c.*1016T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 779,484 control chromosomes in the GnomAD database, including 2,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.063 ( 435 hom., cov: 32)

Exomes 𝑓: 0.082 ( 2500 hom. )

Consequence

ROR2
NM_004560.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.315

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 -14 ACMG points.

BP4

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

BP6

Variant 9-91722646-A-C is Benign according to our data. Variant chr9-91722646-A-C is described in ClinVar as [Benign]. Clinvar id is 367479.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 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.*1016T>G		3_prime_UTR_variant	9/9	ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
ROR2	ENST00000375708.4 linkuse as main transcript	c.*1016T>G	3_prime_UTR_variant	9/9	1	NM_004560.4	P1
ROR2	ENST00000375715.5 linkuse as main transcript	c.1921-66T>G	intron_variant		1
ROR2	ENST00000550066.5 linkuse as main transcript	n.4316T>G	non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9586

AN:

152110

Hom.:

429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0937

Gnomad ASJ

AF:

0.0570

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0674

Gnomad OTH

AF:

0.0786

GnomAD4 exome

AF:

0.0821

AC:

51482

AN:

627256

Hom.:

2500

Cov.:

AF XY:

0.0828

AC XY:

28312

AN XY:

341774

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.0562

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.0676

Gnomad4 OTH exome

AF:

0.0766

GnomAD4 genome

AF:

0.0631

AC:

9603

AN:

152228

Hom.:

435

Cov.:

AF XY:

0.0669

AC XY:

4981

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.0938

Gnomad4 ASJ

AF:

0.0570

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.0675

Gnomad4 OTH

AF:

0.0863

Alfa

AF:

0.0650

Hom.:

Bravo

AF:

0.0576

Asia WGS

AF:

0.147

AC:

511

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.88

Cadd

Benign

3.3

Dann

Benign

0.63

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