rs10992123

Variant names:

• chr9-91820591-G-A
• rs10992123
• NM_004560.4:c.98-44773C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-91820591-G-A
• chr9-91820591-G-C
• chr9-91820591-G-T

Variant summary

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

The NM_004560.4(ROR2):​c.98-44773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 148,682 control chromosomes in the GnomAD database, including 4,864 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 (4864 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.98-44773C>T		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.98-44773C>T		intron_variant	Intron 1 of 8	1	NM_004560.4	ENSP00000364860.3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 36370 AN: 148548 Hom.: 4854 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.245 AC: 36396 AN: 148682 Hom.: 4864 Cov.: 32 AF XY: 0.252 AC XY: 18313 AN XY: 72574

African (AFR) AF: 0.165 AC: 6710 AN: 40768

American (AMR) AF: 0.421 AC: 6365 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 656 AN: 3420

East Asian (EAS) AF: 0.376 AC: 1825 AN: 4854

South Asian (SAS) AF: 0.255 AC: 1129 AN: 4434

European-Finnish (FIN) AF: 0.310 AC: 3082 AN: 9952

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.236 AC: 15804 AN: 66874

Other (OTH) AF: 0.251 AC: 521 AN: 2078

Alfa AF: 0.125 Hom.: 214

Bravo AF: 0.248

Asia WGS AF: 0.291 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10992123; hg19: chr9-94582873;