rs9852153

chr3-146106113-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182943.3(PLOD2):c.615+419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,104 control chromosomes in the GnomAD database, including 16,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (16727 hom., cov: 33)
• Consequence: PLOD2 NM_182943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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	UniProt
PLOD2	NM_182943.3	c.615+419A>G		intron_variant		ENST00000282903.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLOD2	ENST00000282903.10	c.615+419A>G		intron_variant		1	NM_182943.3	P3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70991 AN: 151984 Hom.: 16717 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.467 AC: 71036 AN: 152104 Hom.: 16727 Cov.: 33 AF XY: 0.466 AC XY: 34683 AN XY: 74360

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.475

Alfa AF: 0.463 Hom.: 2019

Bravo AF: 0.472

Asia WGS AF: 0.482 AC: 1678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9852153; hg19: chr3-145823900;