chr9-91948565-C-A

Position:

• chr9-91948565-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ROR2	NM_004560.4	c.97+1302G>T		intron_variant		ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.97+1302G>T		intron_variant		1	NM_004560.4	ENSP00000364860	P1

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

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.349

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

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.386

Alfa AF: 0.344 Hom.: 9011

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9774945; hg19: chr9-94710847;