rs10992158

Variant names:

• chr9-91912645-T-C
• rs10992158
• NM_004560.4:c.97+37222A>G

Variant summary

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

The NM_004560.4(ROR2):​c.97+37222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,152 control chromosomes in the GnomAD database, including 4,897 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 0.24 (4897 hom., cov: 33)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.97+37222A>G		intron_variant	Intron 1 of 8	ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.97+37222A>G		intron_variant	Intron 1 of 8	1	NM_004560.4	ENSP00000364860.3
ROR2	ENST00000375715.5	c.-324+35962A>G		intron_variant	Intron 1 of 12	1		ENSP00000364867.1
ROR2	ENST00000495386.5	n.234+11120A>G		intron_variant	Intron 2 of 4	3
ROR2	ENST00000546883.1	n.299+11120A>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35948 AN: 152034 Hom.: 4890 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.236 AC: 35963 AN: 152152 Hom.: 4897 Cov.: 33 AF XY: 0.244 AC XY: 18120 AN XY: 74386

African (AFR) AF: 0.126 AC: 5233 AN: 41528

American (AMR) AF: 0.424 AC: 6479 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3472

East Asian (EAS) AF: 0.375 AC: 1940 AN: 5178

South Asian (SAS) AF: 0.255 AC: 1228 AN: 4824

European-Finnish (FIN) AF: 0.274 AC: 2894 AN: 10552

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16581 AN: 67990

Other (OTH) AF: 0.227 AC: 478 AN: 2110

Alfa AF: 0.244 Hom.: 2273

Bravo AF: 0.246

Asia WGS AF: 0.303 AC: 1050 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.85
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10992158; hg19: chr9-94674927;