rs11790808

Positions:

• chr9-91826216-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004560.4(ROR2):​c.98-50398A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 152,248 control chromosomes in the GnomAD database, including 152 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 0.037 (152 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR2	NM_004560.4	c.98-50398A>G		intron_variant		ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375708.4	c.98-50398A>G		intron_variant		1	NM_004560.4	P1

Frequencies

GnomAD3 genomes AF: 0.0370 AC: 5633 AN: 152130 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0480

Gnomad OTH AF: 0.0445

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0370 AC: 5630 AN: 152248 Hom.: 152 Cov.: 32 AF XY: 0.0363 AC XY: 2702 AN XY: 74434

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.0333

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.0612

Gnomad4 FIN AF: 0.0321

Gnomad4 NFE AF: 0.0480

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0472 Hom.: 239

Bravo AF: 0.0354

Asia WGS AF: 0.0780 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.034
DANN	Benign	0.45

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: rs11790808; hg19: chr9-94588498;