9-91800399-T-C

Variant names:

• chr9-91800399-T-C
• rs7029814
• NM_004560.4:c.98-24581A>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.98-24581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,432 control chromosomes in the GnomAD database, including 23,485 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 0.50 (23485 hom., cov: 30)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.98-24581A>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.98-24581A>G		intron_variant	Intron 1 of 8	1	NM_004560.4	ENSP00000364860.3

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76134 AN: 151326 Hom.: 23421 Cov.: 30

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.504 AC: 76262 AN: 151432 Hom.: 23485 Cov.: 30 AF XY: 0.508 AC XY: 37590 AN XY: 73966

African (AFR) AF: 0.857 AC: 35365 AN: 41288

American (AMR) AF: 0.498 AC: 7596 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3470

East Asian (EAS) AF: 0.718 AC: 3688 AN: 5138

South Asian (SAS) AF: 0.399 AC: 1901 AN: 4764

European-Finnish (FIN) AF: 0.400 AC: 4167 AN: 10406

Middle Eastern (MID) AF: 0.392 AC: 112 AN: 286

European-Non Finnish (NFE) AF: 0.308 AC: 20861 AN: 67830

Other (OTH) AF: 0.458 AC: 962 AN: 2100

Alfa AF: 0.378 Hom.: 16799

Bravo AF: 0.529

Asia WGS AF: 0.581 AC: 2020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		-0.61
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: rs7029814; hg19: chr9-94562681;