rs7031729

Variant names:

• chr9-91744648-C-A
• rs7031729
• NM_004560.4:c.495-7130G>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.495-7130G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,024 control chromosomes in the GnomAD database, including 22,239 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 0.54 (22239 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.495-7130G>T		intron_variant	Intron 4 of 8	ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.495-7130G>T		intron_variant	Intron 4 of 8	1	NM_004560.4	ENSP00000364860.3
ROR2	ENST00000375715.5	c.75-7130G>T		intron_variant	Intron 4 of 12	1		ENSP00000364867.1
ROR2	ENST00000550066.5	n.963-7130G>T		intron_variant	Intron 6 of 10	2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81993 AN: 151906 Hom.: 22225 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.540 AC: 82033 AN: 152024 Hom.: 22239 Cov.: 32 AF XY: 0.538 AC XY: 39999 AN XY: 74308

African (AFR) AF: 0.550 AC: 22793 AN: 41464

American (AMR) AF: 0.497 AC: 7596 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1851 AN: 3468

East Asian (EAS) AF: 0.438 AC: 2261 AN: 5166

South Asian (SAS) AF: 0.449 AC: 2165 AN: 4820

European-Finnish (FIN) AF: 0.588 AC: 6206 AN: 10558

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.552 AC: 37532 AN: 67958

Other (OTH) AF: 0.504 AC: 1066 AN: 2114

Alfa AF: 0.540 Hom.: 4309

Bravo AF: 0.535

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.76
DANN	Benign	0.75
PhyloP100		0.084
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: rs7031729; hg19: chr9-94506930;