9-91712589-T-C

Variant names:

• chr9-91712589-T-C
• rs9299397
• ENST00000375715.5:c.2065+4718A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375715.5(ROR2):​c.2065+4718A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 152,174 control chromosomes in the GnomAD database, including 71,943 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 0.97 (71943 hom., cov: 29)
• Consequence: ROR2 ENST00000375715.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• Publications: 2 publications found

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]

ROR2 Gene-Disease associations (from GenCC):

• brachydactyly type B1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive Robinow syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375715.5	c.2065+4718A>G		intron_variant	Intron 11 of 12	1		ENSP00000364867.1

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147821 AN: 152056 Hom.: 71881 Cov.: 29

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.961

Gnomad OTH AF: 0.974

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

GnomAD4 genome AF: 0.972 AC: 147942 AN: 152174 Hom.: 71943 Cov.: 29 AF XY: 0.971 AC XY: 72245 AN XY: 74390

African (AFR) AF: 0.993 AC: 41240 AN: 41522

American (AMR) AF: 0.982 AC: 15022 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3322 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5162 AN: 5162

South Asian (SAS) AF: 0.940 AC: 4515 AN: 4804

European-Finnish (FIN) AF: 0.951 AC: 10073 AN: 10588

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.961 AC: 65373 AN: 68008

Other (OTH) AF: 0.974 AC: 2059 AN: 2114

Alfa AF: 0.968 Hom.: 8998

Bravo AF: 0.976

Asia WGS AF: 0.981 AC: 3411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9299397; hg19: chr9-94474871;