rs121909086
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004560.4(ROR2):c.613C>T(p.Arg205Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000274 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ROR2
NM_004560.4 stop_gained
NM_004560.4 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 6.74
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-91737400-G-A is Pathogenic according to our data. Variant chr9-91737400-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 7310.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-91737400-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROR2 | NM_004560.4 | c.613C>T | p.Arg205Ter | stop_gained | 5/9 | ENST00000375708.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROR2 | ENST00000375708.4 | c.613C>T | p.Arg205Ter | stop_gained | 5/9 | 1 | NM_004560.4 | P1 | |
ROR2 | ENST00000375715.5 | c.193C>T | p.Arg65Ter | stop_gained | 5/13 | 1 | |||
ROR2 | ENST00000550066.5 | n.1081C>T | non_coding_transcript_exon_variant | 7/11 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727240
GnomAD4 exome
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1461874
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33
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1
AN XY:
727240
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive Robinow syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2000 | - - |
Pathogenic, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at