chr9-91850109-T-C

Variant names:

• chr9-91850109-T-C
• rs7048756
• NM_004560.4:c.98-74291A>G

Variant summary

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

The ENST00000375708.4(ROR2):​c.98-74291A>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 152,042 control chromosomes in the GnomAD database, including 14,139 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 (14139 hom., cov: 32)
• Consequence: ROR2 ENST00000375708.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375708.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	NM_004560.4	MANE Select	c.98-74291A>G		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.98-74291A>G		intron	N/A	NP_001305133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	ENST00000375708.4	TSL:1 MANE Select	c.98-74291A>G		intron	N/A	ENSP00000364860.3
	ROR2	ENST00000375715.5	TSL:1	c.-323-74291A>G		intron	N/A	ENSP00000364867.1
	ROR2	ENST00000495386.5	TSL:3	n.360+33149A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60566 AN: 151924 Hom.: 14106 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.399 AC: 60649 AN: 152042 Hom.: 14139 Cov.: 32 AF XY: 0.403 AC XY: 29961 AN XY: 74330

African (AFR) AF: 0.630 AC: 26121 AN: 41438

American (AMR) AF: 0.489 AC: 7462 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3466

East Asian (EAS) AF: 0.446 AC: 2306 AN: 5166

South Asian (SAS) AF: 0.316 AC: 1521 AN: 4816

European-Finnish (FIN) AF: 0.308 AC: 3258 AN: 10578

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17992 AN: 67984

Other (OTH) AF: 0.361 AC: 764 AN: 2114

Alfa AF: 0.329 Hom.: 1637

Bravo AF: 0.425

Asia WGS AF: 0.402 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-0.53
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: rs7048756; hg19: chr9-94612391;