rs9289716
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_182943.3(PLOD2):c.503-47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 915,488 control chromosomes in the GnomAD database, including 100,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.48 ( 17407 hom., cov: 32)
Exomes 𝑓: 0.46 ( 83132 hom. )
Consequence
PLOD2
NM_182943.3 intron
NM_182943.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00700
Genes affected
PLOD2 (HGNC:9082): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) The protein encoded by this gene is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VIB have deficiencies in lysyl hydroxylase activity. Mutations in the coding region of this gene are associated with Bruck syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 3-146106691-A-G is Benign according to our data. Variant chr3-146106691-A-G is described in ClinVar as [Benign]. Clinvar id is 674924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLOD2 | NM_182943.3 | c.503-47T>C | intron_variant | ENST00000282903.10 | NP_891988.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLOD2 | ENST00000282903.10 | c.503-47T>C | intron_variant | 1 | NM_182943.3 | ENSP00000282903.5 |
Frequencies
GnomAD3 genomes AF: 0.477 AC: 72401AN: 151874Hom.: 17399 Cov.: 32
GnomAD3 genomes
AF:
AC:
72401
AN:
151874
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.467 AC: 115638AN: 247412Hom.: 27465 AF XY: 0.468 AC XY: 62791AN XY: 134072
GnomAD3 exomes
AF:
AC:
115638
AN:
247412
Hom.:
AF XY:
AC XY:
62791
AN XY:
134072
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.463 AC: 353557AN: 763494Hom.: 83132 Cov.: 10 AF XY: 0.464 AC XY: 189121AN XY: 407384
GnomAD4 exome
AF:
AC:
353557
AN:
763494
Hom.:
Cov.:
10
AF XY:
AC XY:
189121
AN XY:
407384
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.477 AC: 72442AN: 151994Hom.: 17407 Cov.: 32 AF XY: 0.475 AC XY: 35308AN XY: 74296
GnomAD4 genome
AF:
AC:
72442
AN:
151994
Hom.:
Cov.:
32
AF XY:
AC XY:
35308
AN XY:
74296
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1684
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Bruck syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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