rs7871522

chr9-91941579-G-Achr9-91941579-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004560.4(ROR2):c.97+8288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,994 control chromosomes in the GnomAD database, including 4,731 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 0.24 (4731 hom., cov: 31)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR2	NM_004560.4	c.97+8288C>T		intron_variant		ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375708.4	c.97+8288C>T		intron_variant		1	NM_004560.4	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36754 AN: 151876 Hom.: 4716 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.242 AC: 36802 AN: 151994 Hom.: 4731 Cov.: 31 AF XY: 0.241 AC XY: 17893 AN XY: 74308

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.0956

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.234

Alfa AF: 0.258 Hom.: 855

Bravo AF: 0.240

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.9
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7871522; hg19: chr9-94703861;