chr9-91723109-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004560.4(ROR2):c.*553G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000679 in 160,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00096 ( 0 hom. )
Consequence
ROR2
NM_004560.4 3_prime_UTR
NM_004560.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.54
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ROR2 | NM_004560.4 | c.*553G>A | 3_prime_UTR_variant | 9/9 | ENST00000375708.4 | NP_004551.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ROR2 | ENST00000375708.4 | c.*553G>A | 3_prime_UTR_variant | 9/9 | 1 | NM_004560.4 | ENSP00000364860 | P1 | ||
ROR2 | ENST00000375715.5 | c.1921-529G>A | intron_variant | 1 | ENSP00000364867 | |||||
ROR2 | ENST00000550066.5 | n.3853G>A | non_coding_transcript_exon_variant | 11/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000664 AC: 101AN: 152138Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000959 AC: 8AN: 8346Hom.: 0 Cov.: 0 AF XY: 0.00135 AC XY: 6AN XY: 4442
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GnomAD4 genome AF: 0.000663 AC: 101AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.000564 AC XY: 42AN XY: 74438
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive Robinow syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Brachydactyly type B1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at