9-91722896-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_004560.4(ROR2):c.*766T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000063 in 428,364 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
ROR2
NM_004560.4 3_prime_UTR
NM_004560.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.93
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 was made for transcript
Our verdict: Benign. The variant received -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 9-91722896-A-G is Benign according to our data. Variant chr9-91722896-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 367482.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000058 (16/275990) while in subpopulation MID AF = 0.00324 (4/1236). AF 95% confidence interval is 0.00111. There are 0 homozygotes in GnomAdExome4. There are 7 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position FAILED quality control check.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ROR2 | ENST00000375708 | c.*766T>C | 3_prime_UTR_variant | Exon 9 of 9 | 1 | NM_004560.4 | ENSP00000364860.3 | |||
ROR2 | ENST00000375715.5 | c.1921-316T>C | intron_variant | Intron 9 of 12 | 1 | ENSP00000364867.1 | ||||
ROR2 | ENST00000550066.5 | n.4066T>C | non_coding_transcript_exon_variant | Exon 11 of 11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000722 AC: 11AN: 152256Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
11
AN:
152256
Hom.:
Cov.:
33
Gnomad AFR
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GnomAD4 exome AF: 0.0000580 AC: 16AN: 275990Hom.: 0 Cov.: 0 AF XY: 0.0000489 AC XY: 7AN XY: 143030 show subpopulations
GnomAD4 exome
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16
AN:
275990
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0
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7
AN XY:
143030
Gnomad4 AFR exome
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0
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9198
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1
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13340
Gnomad4 ASJ exome
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0
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8886
Gnomad4 EAS exome
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0
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18992
Gnomad4 SAS exome
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0
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27942
Gnomad4 FIN exome
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0
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14302
Gnomad4 NFE exome
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AC:
9
AN:
165648
Gnomad4 Remaining exome
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AC:
2
AN:
16446
Heterozygous variant carriers
0
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Allele balance
Exome Het
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Age
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152374Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74518 show subpopulations
GnomAD4 genome
AF:
AC:
11
AN:
152374
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33
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6
AN XY:
74518
Gnomad4 AFR
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0
Gnomad4 AMR
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0.000392054
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0.000392054
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0
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0
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0
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0
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0
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0
Gnomad4 NFE
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AC:
0.0000587924
AN:
0.0000587924
Gnomad4 OTH
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0
AN:
0
Heterozygous variant carriers
0
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2
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Allele balance
Genome Het
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant Robinow syndrome 1 Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Brachydactyly Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at