rs4681294

chr3-146077353-G-A

Variant summary

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

The NM_182943.3(PLOD2):c.1564-458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 179,440 control chromosomes in the GnomAD database, including 19,439 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 0.46 (16437 hom., cov: 32)
  • Exomes 𝑓: 0.46 (3002 hom.)
• Consequence: PLOD2 NM_182943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLOD2	NM_182943.3	c.1564-458C>T		intron_variant		ENST00000282903.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLOD2	ENST00000282903.10	c.1564-458C>T		intron_variant		1	NM_182943.3	P3
	ENST00000480247.1	n.337+9175G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70275 AN: 151280 Hom.: 16431 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.458 AC: 12852 AN: 28042 Hom.: 3002 Cov.: 4 AF XY: 0.463 AC XY: 6682 AN XY: 14428

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.464 AC: 70315 AN: 151398 Hom.: 16437 Cov.: 32 AF XY: 0.464 AC XY: 34336 AN XY: 73998

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.474

Alfa AF: 0.455 Hom.: 2671

Bravo AF: 0.468

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.26
Dann	Benign	0.42

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: rs4681294; hg19: chr3-145795140;