rs10992149

chr9-91886397-G-Achr9-91886397-G-C

Variant summary

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

The NM_004560.4(ROR2):c.97+63470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,980 control chromosomes in the GnomAD database, including 6,500 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 (6500 hom., cov: 31)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR2	NM_004560.4	c.97+63470C>T		intron_variant		ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375708.4	c.97+63470C>T		intron_variant		1	NM_004560.4	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43302 AN: 151862 Hom.: 6492 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.285 AC: 43328 AN: 151980 Hom.: 6500 Cov.: 31 AF XY: 0.292 AC XY: 21664 AN XY: 74266

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.278

Alfa AF: 0.261 Hom.: 673

Bravo AF: 0.298

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs10992149; hg19: chr9-94648679;