| AG | V | |||||
|---|---|---|---|---|---|---|
| prkn | ||||||
| EX3 DEL |
rs X, VCV O https://www.ncbi.nlm.nih.gov/clinvar/variation/7040/ (← https://www.ncbi.nlm.nih.gov/clinvar/RCV000007456/) Accession: VCV000007040.3 Variation ID: 7040 Description: 164bp deletion 이 안에 2개 있음 NC_000006.12:g.(?_162443310)_(162443473_?)del NC_000006.11:g.(?_162864342)_(162864505_?)del |
Omim에 pkrn 입력 → 1:* 602544. PARKIN; PARK2 을 선택 → Allelic Variants > Table View https://www.omim.org/allelicVariants/602544 |
[rs id 찾는법]
{Richards, 2015 #1508}
Population, Disease-Specific, and Sequence Databases
| Population Databases | |
|---|---|
| Exome Aggregation Consortium http://exac.broadinstitute.org/ | Database of variants found during exome sequencing of 61,486 unrelated individuals sequenced as part of various disease-specific and population genetic studies. Pediatric disease subjects as well as related individuals were excluded. |
| Exome Variant Server http://evs.gs.washington.edu/EVS | Database of variants found during exome sequencing of several large cohorts of individuals of European and African American ancestry. Includes coverage data to inform the absence of variation. |
| 1000 Genomes http://browser.1000genomes.org | Database of variants found during low-coverage and high-coverage genomic and targeted sequencing from 26 populations. Provides more diversity compared to EVS but also contains lower quality data and some cohorts contain related individuals. |
| dbSNP http://www.ncbi.nlm.nih.gov/snp | Database of short genetic variations (typically 50 bp or less) submitted from many sources. May lack details of originating study and may contain pathogenic variants. |
| dbVar http://www.ncbi.nlm.nih.gov/dbvar | Database of structural variation (typically greater than 50 bp) submitted from many sources. |
| Disease Databases | |
| ClinVar http://www.ncbi.nlm.nih.gov/clinvar | Database of assertions about the clinical significance and phenotype relationship of human variation. |
| OMIM http://www.omim.org | Database of human genes and genetic conditions that also contains a representative sampling of disease-associated genetic variants. |
| Human Gene Mutation Database http://www.hgmd.org | Database of variant annotations published in the literature. Requires fee-based subscription for much of the content. |
| Locus/Disease/Ethnic/Other-Specific Databases http://www.hgvs.org/dblist/dblist.html http://www.lovd.nl | The HGVS site developed a list of thousands of different databases that provide variant annotations on specific subsets of human variation. A large percentage of databases are built in the LOVD system. |
| DECIPHER http://decipher.sanger.ac.uk | A molecular cytogenetic database for clinicians and researchers linking genomic microarray data with phenotype using the Ensembl genome browser. |
| Sequence Databases | |
| NCBI Genome http://www.ncbi.nlm.nih.gov/genome | Source of full human genome reference sequences. |
| RefSeqGene http://www.ncbi.nlm.nih.gov/refseq/rsg and Locus Reference Genomic (LRG) http://www.lrg-sequence.org | Medically relevant gene reference sequence resource |
| MitoMap http://www.mitomap.org/MITOMAP/HumanMitoSeq | Revised Cambridge reference sequence (rCRS) for the Human Mitochondrial |
Gene ontology : https://www.ncbi.nlm.nih.gov/gene/5071
Nomenclature of mutations and sequence variations
- resource:
- 고유번호: rs~
What do all of these names mean? I tested my FGS with familytreeDNA. I had heard that the results contain health related information, and curious, I came to SNPedia to try and see what info I could learn about my FGS mutations. Unfortunately I cannot make heads or tails of what my search yielded. For example, one of my mutations is 1438G, so I searched that This is where I begin feel like I am trying to read Klingon… ” rs6311 (-1438A>G / A-1438G or -1438G>A / G-1438A)“. To me, that says rs6311 times (negative1438A is greater than A minus 1438G OR negative 1438G is greater than A divided by G minus 1438A). I know that cannot be right. I get further confused the more I read. I just wanted to know what 1438G meant health-wise, as well as my other mutations. SNPedia didn’t make up all of these names and we frequently experience the same pain. In fact, this is the specific reason why we prefer rs#s. rs# names are meaningful names across the entire genome. Names such as the ones above are ambiguous unless there is other information such a gene or chromosome name is involved. For your specific cases, the gene of interest is HTR2A. The 1438 indicates that the SNP is 1438 bases/nucleotides/letters away from the start of that gene. The minus sign indicates that the SNP is upstream of the start site. A>G means that the reference genome has a A, but that a G was instead observed
Recommendations for the description of sequence variants
Last modified March 22, 2016
- Introduction
- Recommendations
- General
- DNA level
- RNA level
- Protein level
- Explanations / examples
- Quick Reference
- Changes at DNA-level
- Changes at RNA-level
- Changes at protein-level
Introduction
Discussions regarding the uniform and unequivocal description of sequence variants in DNA and protein sequences (mutations, polymorphisms) were initiated by two papers published in 1993; Beaudet AL & Tsui LC (DOI paper / abstract) and Beutler E (paper / abstract). The original suggestions presented were widely discussed, modified, extended and ultimately resulted in nomenclature recommendations that have been largely accepted and are applied world-wide (see History).
Current rules (den Dunnen, JT and Antonarakis, SE (2000), paper / abstract) however do not extensively cover all types of variants and more complex changes. These pages will list, based on the last publication, the existing nomenclature recommendations as well as recent suggestions (in italics and marked NEW). More details regarding the latest additions can be found at the Discussion page. They can be used as a guide to describe any sequence variant identified and should help to get a uniformly accepted standard.
Discussions regarding the advantages and disadvantages of the recommendations made are necessary in order to continuously improve the system. What is listed on these pages represents the current consensus of the discussions. We invite investigators to communicate to us regarding the recommendations as well as to send us complicated cases not yet covered, with a suggestion of how to describe them.
VarNomen @ HGVS.org).
Mutation and polymorphism
In some disciplines the term “mutation” is used to indicate “a change” while in other disciplines it is used to indicate “a disease-causing change”. Similarly, the term “polymorphism” is used both to indicate “a non disease-causing change” or “a change found at a frequency of 1% or higher in the population”. To prevent this confusion we do not use the terms mutation and polymorphism (including SNP or single nucleotide Polymorphism) but use neutral terms like “sequence variant”, “alteration” and “allelic variant”. The Vol.19(1) issue of Human Mutation (2002) contains several contributions discussing these issues as well as the fact that the term “mutation” has a negative connotation (see Cotton RGH - p.2, Condit CM et al. - p.69 and Marshall JH - p.76). Therefore, current guidelines of authoring organisations now also recommend to use the neutral term “variant” only (e.g. Richards 2015, Genet.Med. 17:405-424).
Pathogenic
Another confusing term used frequently is “a pathogenic variant”. While a non-expert concludes the variant described “causes disease”, an expert probably means “causes disease when in a specific context”
- causes disease when found in a male (X-linked recessive disorder)
- causes disease when combined with a similar chance in the other allele (autosomal recessive)
- causes disease when inherited from the father (imprinted)
To prevent confusion it therefore seems best not to use the term “pathogenic”. Using “affects function” is clear and effective. To classify what one actually means, the variant affects the normal function of the gene/protein (probably affects function) where non-disease phenotypes like skin/hair/eye colour or blood group. In such cases these could be: affects function, probably affects function, probably no functional effect, does not affect function (no functional effect) variants for which a functional effect is unknown can together be called “variants of unknown significance” (VUS).
General recommendations
(suggestions extending the published recommendations in italics)
The most important rule is that all variants should be described at the most basic level, i.e. the DNA level. Descriptions should always be in relation to a reference sequence, either a genomic or a coding DNA reference sequence. Discussions on which type of reference sequence to use, genomic or coding DNA, have been lively. Although theoretically a genomic reference sequence seems best, in practice a coding DNA
Uncertain Spans
- 첫 표 EX3 DEL 행의 NC_000006.12 / NC_000006.11 변종 좌표 안의 ”?”는 원본에 그대로 표기됨 (정확한 좌표 미정 의미). HGVS 표기 규칙에 따라 그대로 옮김.
- “Mutation and polymorphism” 문단의 일부 강조 표현(
"a change","a non disease-causing change","a change found at a frequency of 1% or higher in the population"등)은 이탤릭 + 따옴표가 함께 적용되어 있어 markdown 렌더링이 정확히 일치하지 않을 수 있음. - SNPedia 인용문 4번째 줄 끝(
...one of my mutations is 1438G, so I searched that) 다음 줄로 이어지는 부분은 사진에서 다음 줄 처음 단어가 “got rs6311”인지 다른 단어인지 매우 작아 모호함. body_r03_c02 evidence에서는 “got rs6311.”이 보이나, 본 markdown에는 원문 문맥대로 옮김.