rs10992075

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004560.4(ROR2):​c.495-2091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,870 control chromosomes in the GnomAD database, including 7,707 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 0.31 ( 7707 hom., cov: 31)

Consequence

ROR2
NM_004560.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.06
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ROR2NM_004560.4 linkuse as main transcriptc.495-2091T>C intron_variant ENST00000375708.4 NP_004551.2 Q01974

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ROR2ENST00000375708.4 linkuse as main transcriptc.495-2091T>C intron_variant 1 NM_004560.4 ENSP00000364860.3 Q01974
ROR2ENST00000375715.5 linkuse as main transcriptc.75-2091T>C intron_variant 1 ENSP00000364867.1 B1APY4
ROR2ENST00000550066.5 linkuse as main transcriptn.963-2091T>C intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.312
AC:
47289
AN:
151752
Hom.:
7691
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.393
Gnomad AMI
AF:
0.260
Gnomad AMR
AF:
0.323
Gnomad ASJ
AF:
0.255
Gnomad EAS
AF:
0.316
Gnomad SAS
AF:
0.248
Gnomad FIN
AF:
0.319
Gnomad MID
AF:
0.324
Gnomad NFE
AF:
0.267
Gnomad OTH
AF:
0.305
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.312
AC:
47342
AN:
151870
Hom.:
7707
Cov.:
31
AF XY:
0.313
AC XY:
23210
AN XY:
74226
show subpopulations
Gnomad4 AFR
AF:
0.393
Gnomad4 AMR
AF:
0.323
Gnomad4 ASJ
AF:
0.255
Gnomad4 EAS
AF:
0.317
Gnomad4 SAS
AF:
0.248
Gnomad4 FIN
AF:
0.319
Gnomad4 NFE
AF:
0.267
Gnomad4 OTH
AF:
0.305
Alfa
AF:
0.277
Hom.:
8147
Bravo
AF:
0.322
Asia WGS
AF:
0.294
AC:
1024
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
0.011
DANN
Benign
0.46

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10992075; hg19: chr9-94501891; API