rs148340413
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004560.4(ROR2):c.730C>T(p.Arg244Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000376 in 1,612,308 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R244P) has been classified as Uncertain significance.
Frequency
Consequence
NM_004560.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROR2 | NM_004560.4 | c.730C>T | p.Arg244Trp | missense_variant | 6/9 | ENST00000375708.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROR2 | ENST00000375708.4 | c.730C>T | p.Arg244Trp | missense_variant | 6/9 | 1 | NM_004560.4 | P1 | |
ROR2 | ENST00000375715.5 | c.310C>T | p.Arg104Trp | missense_variant | 6/13 | 1 | |||
ROR2 | ENST00000550066.5 | n.1198C>T | non_coding_transcript_exon_variant | 8/11 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000440 AC: 67AN: 152238Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000668 AC: 165AN: 247100Hom.: 2 AF XY: 0.000864 AC XY: 116AN XY: 134274
GnomAD4 exome AF: 0.000370 AC: 540AN: 1459952Hom.: 6 Cov.: 35 AF XY: 0.000483 AC XY: 351AN XY: 726324
GnomAD4 genome ? AF: 0.000433 AC: 66AN: 152356Hom.: 1 Cov.: 33 AF XY: 0.000550 AC XY: 41AN XY: 74502
ClinVar
Submissions by phenotype
Autosomal recessive Robinow syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | The ROR2 c.730C>T (p.Arg244Trp) variant has been reported in one patient in a homozygous state (Ali et al. 2007). The variant was absent from 50 ethnically matched controls but is reported at a frequency of 0.00409 in the South Asian population in the 1000 Genomes Project. Functional studies using transfected HeLa cells demonstrated that the variant protein localized to the endoplasmic reticulum while the wild type protein localized in the plasma membrane (Ali et al. 2007). Based on the evidence, the p.Arg244Trp variant is classified as a variant of unknown significance but suspicious for pathogenicity for Robinow syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Likely benign, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Dec 29, 2019 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | ROR2: BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 21, 2018 | - - |
Brachydactyly type B1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at