rs7874148

Positions:

• chr9-91832093-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.98-56275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,796 control chromosomes in the GnomAD database, including 14,150 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 0.40 (14150 hom., cov: 30)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR2	NM_004560.4	c.98-56275A>G		intron_variant		ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.98-56275A>G		intron_variant		1	NM_004560.4	ENSP00000364860	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60522 AN: 151678 Hom.: 14129 Cov.: 30

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.337

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.399 AC: 60593 AN: 151796 Hom.: 14150 Cov.: 30 AF XY: 0.403 AC XY: 29925 AN XY: 74164

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.361

Alfa AF: 0.309 Hom.: 5591

Bravo AF: 0.425

Asia WGS AF: 0.400 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.059
DANN	Benign	0.32

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: rs7874148; hg19: chr9-94594375;