rs10992124

Positions:

• chr9-91822170-C-A
• chr9-91822170-C-G
• chr9-91822170-C-T

Variant summary

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

The ENST00000375708.4(ROR2):​c.98-46352G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,098 control chromosomes in the GnomAD database, including 6,946 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 0.29 (6946 hom., cov: 33)
• Consequence: ROR2 ENST00000375708.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR2	NM_004560.4	c.98-46352G>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.98-46352G>T		intron_variant		1	NM_004560.4	ENSP00000364860	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44734 AN: 151980 Hom.: 6919 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.295 AC: 44797 AN: 152098 Hom.: 6946 Cov.: 33 AF XY: 0.299 AC XY: 22269 AN XY: 74368

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.295

Alfa AF: 0.227 Hom.: 1110

Bravo AF: 0.309

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
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

Other links and lift over

dbSNP: rs10992124; hg19: chr9-94584452;