9-91886978-A-T

Variant names:

• chr9-91886978-A-T
• rs7021744
• NM_004560.4:c.97+62889T>A

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+62889T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,938 control chromosomes in the GnomAD database, including 33,000 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 0.64 (32996 hom., cov: 31)
  • Exomes 𝑓: 0.64 (4 hom.)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.97+62889T>A		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+62889T>A		intron_variant	Intron 1 of 8	1	NM_004560.4	ENSP00000364860.3

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96810 AN: 151798 Hom.: 32939 Cov.: 31

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.609

GnomAD4 exome AF: 0.636 AC: 14 AN: 22 Hom.: 4 Cov.: 0 AF XY: 0.625 AC XY: 10 AN XY: 16

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 9 AN: 12

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.638 AC: 96922 AN: 151916 Hom.: 32996 Cov.: 31 AF XY: 0.640 AC XY: 47451 AN XY: 74194

African (AFR) AF: 0.887 AC: 36781 AN: 41476

American (AMR) AF: 0.663 AC: 10117 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1817 AN: 3466

East Asian (EAS) AF: 0.609 AC: 3112 AN: 5110

South Asian (SAS) AF: 0.562 AC: 2710 AN: 4820

European-Finnish (FIN) AF: 0.556 AC: 5854 AN: 10530

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34597 AN: 67940

Other (OTH) AF: 0.610 AC: 1288 AN: 2112

Alfa AF: 0.590 Hom.: 3476

Bravo AF: 0.656

Asia WGS AF: 0.628 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.71
PhyloP100		-1.3
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: rs7021744; hg19: chr9-94649260;