Korean YOPD / PRKN ClinVar And OMIM Allelic Variant Notes

Korean YOPD / PARK2 Mutation Frequency Notes

Top clipped fragment from the previous row:

patients: two young onset (YO, 49세이하), 32 middle onset (MO, 50-69) and 49 late onset (LO, 70세 이상).

YOPD row:

YOPD
 
The frequency of PARK2 mutation has been reported in the 5.5-15.8 % of the Korean population with early onset PD (EOPD) (Choi et al. 2008; Chu et al. 2014; Kim et al. 2012).

Reference notes:

citation	visible note
(Choi, 2008 #1351)	한림대
(Chu, 2014 #1353)	한림대+?; (erratum존재)
(Kim, 2012 #1354)	전범석 서울대 n=114

Methods/summary fragments:

Methods: 189 patients with early-onset PD or familial PD, and 191 control individuals
다양한 Exon deletion이 많음. We identified 22 PD patients with PARK2 mutations (11.6%).
Five patients (2.6%) had compound heterozygous mutations, and 13 patients (6.9%) had a heterozygous mutation. The phase could not be determined in one patient. Three small sequence variations were found in 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90% of all of the mutations found.

14 different PARK2 mutations (3 point mutations plus 11 exon rearrangements) were identified in 18 patients, comprising 1 homozygote (0.9%), 13 compound heterozygotes (11.4%), 3 single heterozygotes (2.6%), and 1 with unknown phase (0.9%).
- We identified 20 alleles with single exon rearrangement and nine alleles with multi-exon rearrangement. Exon rearrangements were clustered between exons 2 and 6, and single deletions of exon 3 or 4 and contiguous exon 3-4 deletions were most common in this population.

ClinVar / OMIM PRKN Allelic Variants

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar)
OMIM https://www.omim.org/allelicVariants/602544
602544 PARKIN; PARK2
Allelic Variants (23 Selected Examples):
All ClinVar Variants

Table columns:

Number | Phenotype | Mutation | [change / note] | [clinical significance] | SNP | gnomAD | ClinVar

Row fragments:

no.	phenotype	mutation	change / note	significance	SNP	gnomAD	ClinVar
.0001	PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE	PARK2, EX3-7DEL			-	-	RCV000007450
.0002	same phenotype	PARK2, EX4DEL			-	-	RCV000007451
.0003	same phenotype	PARK2, THR240ARG	G>A,C,T	conflicting-interpretations-of-pathogenicity.pathogenic	rs137853054	rs137853054?	RCV000007452
.0004	same phenotype	PARK2, GLN311TER	G>A	pathogenic	rs137853055	-	RCV000007453
.0005	same phenotype	PARK2, EX3DEL			-	-	RCV000007456에서 다음으로 변경 Accession: VCV000007040.3
.0006	same phenotype	PARK2, EX8-9DEL			-	-	RCV000007457
.0007	same phenotype	PARK2, TRP453TER	C>T	likely-pathogenic,pathogenic	rs137853056	-	RCV000007458...
.0008	same phenotype	PARK2, LYS161ASN	T>A	pathogenic	rs137853057	-	RCV000007459
.0009	same phenotype	PARK2, 1-BP DEL, 202A			-	-	RCV000007460
.0010	same phenotype	PARK2, EX7DEL			-	-	RCV000007461
.0011	same phenotype	PARK2, ALA82GLU	G>A,T	pathogenic,uncertain-significance,conflicting-interpretations-of-pathogenicity	rs55774500	rs55774500	RCV000007454...
.0012	same phenotype	PARK2, CYS212TYR	C>T	pathogenic	rs137853058	rs137853058	RCV001034684...
.0013	same phenotype	PARK2, VAL56GLU	A>T	uncertain-significance	rs137853059	rs137853059	RCV000007463
.0014	same phenotype	PARK2, 1-BP DEL, 255A			-	-	RCV000007464
.0015	ADENOCARCINOMA OF LUNG, SOMATIC	PARK2, EX2DEL			-	-	RCV000007465
.0016	OVARIAN CANCER, SOMATIC	PARK2, DEL			-	-	RCV000007455
.0017	PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE	PARK2, ARG275TRP	p.Arg275Tryptophan) =R>W, C.823>T, G>A, T	pathogenic	rs34424986	rs34424986	RCV000514660...
.0018	same phenotype	PARK2, LYS211ASN	T>A	pathogenic	rs137853060	rs137853060	RCV000007467
.0019	same phenotype	PARK2, 1-BP DEL, 1072T			-	-	RCV000007468
.0020	same phenotype	PARK2, IVS1DS, G-T,+1	C>A,G	pathogenic	rs397518439	-	RCV000007469
.0021	Same as 0003
.0022	PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE	PARK2, EX5-6DEL			-	-	RCV000007471
.0023	same phenotype	PARK2, CYS431PHE	C>A	pathogenic	rs397514694	-	RCV000043509

Brain Net / ClinVarMiner / Structural Variant Notes

Brain net search line:

Brain net search using: rs137853054, rs137853055, rs137853056, rs137853057, rs55774500, rs137853058, rs137853059, rs34424986, rs137853060, rs397518439, rs137853054, rs397514694 -> 11 HITS but all major alleles

ClinVarMiner note:

중요
https://clinvarminer.genetics.utah.edu/variants-by-gene/PRKN/significance/pathogenic
List of variants in gene PRKN reported as pathogenic: Total variants: 67 (but clinvar 직접가서 보면 i) 101 pathogenic PRKN varaints -> 이중 70 germline, SNP), ii) 42 likely pathogenic (of these, many are schizophrenia)

Lower table headings/fragments:

SVS
dbSNP

Structural-variant / coordinate fragments:

Ch37/hg19 6q26(chr6:162137107-162137163)
Ch37/hg19 6q26(chr6:162614287-162660066)x1
Ch37/hg19 6q26(chr6:162638345-162754162)x0
Ch37/hg19 6q26(chr6:162683557-162683797)x0
NC_000006.11:g.(? 162206784)_(162206960 ?)dup
NC_000006.11:g.(? 162206794)_(162206950 ?)dup
NC_000006.11:g.(? 162394314)_(162475226 ?)dup
NC_000006.11:g.(? 162683547)_(162683807 ?)dup
NC_000006.11:g.(? 162864322)_(162864525 ?)dup
NC_000006.11:g.(? 162864332)_(162864519 ?)dup
NC_000006.12:g.(? 161548844)_(161569426 ?)del
NC_000006.12:g.(? 161569335)_(161569436 ?)del
NC_000006.12:g.(? 161785752)_(161973437 ?)del
NC_000006.12:g.(? 161973292)_(161973427 ?)del
NC_000006.12:g.(? 161973292)_(161973427 ?)dup
NC_000006.12:g.(? 161973292)_(162054184 ?)del
NC_000006.12:g.(? 162054081)_(162054184 ?)del
NC_000006.12:g.(? 162054091)_(162054174 ?)del

Uncertain Spans

• page_label: statusbar reads Page 88 of 94, but adjacent processed Parkin pages use other page counts; confirm whether this is a different document section/view.
• nav_path: inferred as Parkin > Parkin PD; the page content is specifically PRKN/PARK2 ClinVar/OMIM evidence.
• (Chu, 2014 #1353) note after 한림대+ is partially unclear.
• Every row in the OMIM/ClinVar table is uncertain at the identifier level, especially row numbers, RCV/VCV, rs IDs, cDNA/protein strings, and punctuation in G>A,C,T, C.823>T, G-T,+1.
• .0003 gnomAD value may be rs137853054; OCR disagreement makes it uncertain.
• .0005 red note appears to say RCV000007456에서 다음으로 변경 Accession: VCV000007040.3; exact wording and whether the old accession is an RCV or VCV entry need review.
• .0017 has visible p.Arg275Tryptophan) =R>W, C.823>T, G>A, T; punctuation/cDNA notation is uncertain.
• Brain net search line contains rs137853054 twice and says 11 HITS; confirm whether one repeated ID is intended or OCR/visual ambiguity.
• Lower NC_000006 lines are uncertain because underscores, g., coordinate parentheses, ?, del, and dup are visually easy to misread.