rs7874148

Variant names:

• chr9-91832093-T-C
• rs7874148
• NM_004560.4:c.98-56275A>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.98-56275A>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 151,796 control chromosomes in the GnomAD database, including 14,150 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 (14150 hom., cov: 30)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 1 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), PanelApp Australia
• autosomal recessive Robinow syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

ENSG00000299518 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	NM_004560.4	MANE Select	c.98-56275A>G		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.98-56275A>G		intron	N/A	NP_001305133.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	ENST00000375708.4	TSL:1 MANE Select	c.98-56275A>G		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-323-56275A>G		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.98-56275A>G		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60522 AN: 151678 Hom.: 14129 Cov.: 30

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.337

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.399 AC: 60593 AN: 151796 Hom.: 14150 Cov.: 30 AF XY: 0.403 AC XY: 29925 AN XY: 74164

African (AFR) AF: 0.630 AC: 26078 AN: 41410

American (AMR) AF: 0.491 AC: 7492 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 864 AN: 3462

East Asian (EAS) AF: 0.443 AC: 2270 AN: 5126

South Asian (SAS) AF: 0.313 AC: 1503 AN: 4800

European-Finnish (FIN) AF: 0.315 AC: 3319 AN: 10528

Middle Eastern (MID) AF: 0.334 AC: 97 AN: 290

European-Non Finnish (NFE) AF: 0.264 AC: 17931 AN: 67910

Other (OTH) AF: 0.361 AC: 759 AN: 2104

Alfa AF: 0.313 Hom.: 6850

Bravo AF: 0.425

Asia WGS AF: 0.400 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.059
DANN	Benign	0.32
PhyloP100		-2.5
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: rs7874148; hg19: chr9-94594375;