NM_004560.4:c.97+1302G>T

Variant names:

• chr9-91948565-C-A
• rs9774945
• NM_004560.4:c.97+1302G>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.97+1302G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 984,086 control chromosomes in the GnomAD database, including 61,883 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 (12513 hom., cov: 33)
  • Exomes 𝑓: 0.34 (49370 hom.)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 6 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.97+1302G>T		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.97+1302G>T		intron_variant	Intron 1 of 8	1	NM_004560.4	ENSP00000364860.3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60560 AN: 151868 Hom.: 12477 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.382

GnomAD4 exome AF: 0.344 AC: 286181 AN: 832100 Hom.: 49370 Cov.: 27 AF XY: 0.343 AC XY: 131856 AN XY: 384276

African (AFR) AF: 0.501 AC: 7891 AN: 15750

American (AMR) AF: 0.550 AC: 541 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 2158 AN: 5150

East Asian (EAS) AF: 0.419 AC: 1516 AN: 3620

South Asian (SAS) AF: 0.387 AC: 6369 AN: 16446

European-Finnish (FIN) AF: 0.385 AC: 107 AN: 278

Middle Eastern (MID) AF: 0.360 AC: 582 AN: 1616

European-Non Finnish (NFE) AF: 0.338 AC: 257513 AN: 761002

Other (OTH) AF: 0.349 AC: 9504 AN: 27254

GnomAD4 genome AF: 0.399 AC: 60654 AN: 151986 Hom.: 12513 Cov.: 33 AF XY: 0.403 AC XY: 29982 AN XY: 74322

African (AFR) AF: 0.478 AC: 19851 AN: 41486

American (AMR) AF: 0.493 AC: 7531 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2077 AN: 5144

South Asian (SAS) AF: 0.384 AC: 1854 AN: 4822

European-Finnish (FIN) AF: 0.356 AC: 3754 AN: 10548

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22951 AN: 67932

Other (OTH) AF: 0.386 AC: 812 AN: 2106

Alfa AF: 0.363 Hom.: 21659

Bravo AF: 0.412

Asia WGS AF: 0.409 AC: 1423 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.8
DANN	Benign	0.77
PhyloP100		-0.072
PromoterAI		-0.0063	Neutral
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: rs9774945; hg19: chr9-94710847;