9-91773350-A-G

Position:

• chr9-91773350-A-G

Variant summary

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

The NM_004560.4(ROR2):​c.175+2391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,430 control chromosomes in the GnomAD database, including 4,253 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 0.23 (4253 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR2	NM_004560.4	c.175+2391T>C		intron_variant		ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.175+2391T>C		intron_variant		1	NM_004560.4	ENSP00000364860	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34286 AN: 151314 Hom.: 4233 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0927

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.227 AC: 34346 AN: 151430 Hom.: 4253 Cov.: 32 AF XY: 0.229 AC XY: 16973 AN XY: 74024

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.227

Alfa AF: 0.143 Hom.: 399

Bravo AF: 0.239

Asia WGS AF: 0.228 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.40

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: rs7039620; hg19: chr9-94535632;