9-91934672-G-A

Position:

• chr9-91934672-G-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+15195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,976 control chromosomes in the GnomAD database, including 23,272 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 0.52 (23272 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR2	NM_004560.4	c.97+15195C>T		intron_variant		ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375708.4	c.97+15195C>T		intron_variant		1	NM_004560.4	P1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79186 AN: 151860 Hom.: 23220 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.522 AC: 79297 AN: 151976 Hom.: 23272 Cov.: 32 AF XY: 0.523 AC XY: 38810 AN XY: 74254

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.490

Alfa AF: 0.409 Hom.: 12611

Bravo AF: 0.546

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.17

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: rs7037255; hg19: chr9-94696954;