rs1512900

Positions:

• chr3-146134942-G-C
• chr3-146134942-G-T

Variant summary

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

The NM_182943.3(PLOD2):​c.110-10713C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,078 control chromosomes in the GnomAD database, including 20,119 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 0.51 (20119 hom., cov: 33)
• Consequence: PLOD2 NM_182943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLOD2	NM_182943.3	c.110-10713C>G		intron_variant		ENST00000282903.10	NP_891988.1
PLOD2	NM_000935.3	c.110-10713C>G		intron_variant			NP_000926.2
PLOD2	XM_047448320.1	c.110-10713C>G		intron_variant			XP_047304276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLOD2	ENST00000282903.10	c.110-10713C>G		intron_variant		1	NM_182943.3	ENSP00000282903	P3

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77857 AN: 151960 Hom.: 20092 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.512 AC: 77932 AN: 152078 Hom.: 20119 Cov.: 33 AF XY: 0.512 AC XY: 38036 AN XY: 74328

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.519

Alfa AF: 0.496 Hom.: 2279

Bravo AF: 0.515

Asia WGS AF: 0.527 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.90
DANN	Benign	0.47

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: rs1512900; hg19: chr3-145852729;