rs7855522

Positions:

• chr9-91737336-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004560.4(ROR2):​c.622+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,610,388 control chromosomes in the GnomAD database, including 182,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14623 hom., cov: 32)
  • Exomes 𝑓: 0.48 (167940 hom.)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-91737336-G-A is Benign according to our data. Variant chr9-91737336-G-A is described in ClinVar as [Benign]. Clinvar id is 1236286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR2	NM_004560.4	c.622+55C>T		intron_variant		ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.622+55C>T		intron_variant		1	NM_004560.4	ENSP00000364860.3
ROR2	ENST00000375715.5	c.202+55C>T		intron_variant		1		ENSP00000364867.1
ROR2	ENST00000550066.5	n.1090+55C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65202 AN: 151918 Hom.: 14623 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.478 AC: 697136 AN: 1458352 Hom.: 167940 AF XY: 0.477 AC XY: 346137 AN XY: 725692

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.429 AC: 65206 AN: 152036 Hom.: 14623 Cov.: 32 AF XY: 0.430 AC XY: 31963 AN XY: 74308

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.416

Alfa AF: 0.455 Hom.: 2567

Bravo AF: 0.416

Asia WGS AF: 0.394 AC: 1369 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs7855522; hg19: chr9-94499618; COSMIC: COSV65216594;