NM_004560.4:c.97+7675G>C

Variant names:

• chr9-91942192-C-G
• rs10125466
• NM_004560.4:c.97+7675G>C

Variant summary

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

The NM_004560.4(ROR2):​c.97+7675G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,020 control chromosomes in the GnomAD database, including 14,738 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 0.42 (14738 hom., cov: 31)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 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.97+7675G>C		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.97+7675G>C		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.97+7675G>C		intron	N/A	ENSP00000364860.3
	ROR2	ENST00000375715.5	TSL:1	c.-324+6415G>C		intron	N/A	ENSP00000364867.1
	ROR2	ENST00000964760.1		c.97+7675G>C		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64334 AN: 151902 Hom.: 14707 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.424 AC: 64420 AN: 152020 Hom.: 14738 Cov.: 31 AF XY: 0.419 AC XY: 31141 AN XY: 74288

African (AFR) AF: 0.607 AC: 25161 AN: 41460

American (AMR) AF: 0.384 AC: 5860 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1533 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1345 AN: 5174

South Asian (SAS) AF: 0.370 AC: 1780 AN: 4808

European-Finnish (FIN) AF: 0.312 AC: 3291 AN: 10546

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24124 AN: 67978

Other (OTH) AF: 0.403 AC: 852 AN: 2114

Alfa AF: 0.228 Hom.: 460

Bravo AF: 0.436

Asia WGS AF: 0.360 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	9.4
DANN	Benign	0.60
PhyloP100		-0.087
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: rs10125466; hg19: chr9-94704474;