9-91784701-A-T

Variant names:

• chr9-91784701-A-T
• rs4595189
• NM_004560.4:c.98-8883T>A

Variant summary

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

The NM_004560.4(ROR2):​c.98-8883T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,128 control chromosomes in the GnomAD database, including 20,334 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 0.48 (20334 hom., cov: 33)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004560.4. 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.98-8883T>A		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.98-8883T>A		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.98-8883T>A		intron	N/A	ENSP00000364860.3
	ROR2	ENST00000375715.5	TSL:1	c.-323-8883T>A		intron	N/A	ENSP00000364867.1
	ROR2	ENST00000495386.5	TSL:3	n.361-8883T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73574 AN: 152010 Hom.: 20327 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.484 AC: 73583 AN: 152128 Hom.: 20334 Cov.: 33 AF XY: 0.485 AC XY: 36040 AN XY: 74354

African (AFR) AF: 0.218 AC: 9033 AN: 41508

American (AMR) AF: 0.488 AC: 7466 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1768 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1712 AN: 5178

South Asian (SAS) AF: 0.438 AC: 2111 AN: 4816

European-Finnish (FIN) AF: 0.668 AC: 7062 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42678 AN: 67990

Other (OTH) AF: 0.494 AC: 1040 AN: 2106

Alfa AF: 0.553 Hom.: 3114

Bravo AF: 0.461

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.41
PhyloP100		-0.34
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: rs4595189; hg19: chr9-94546983;