3-146117955-T-C

Position:

• chr3-146117955-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.338+3157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,608 control chromosomes in the GnomAD database, including 17,405 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 0.48 (17405 hom., cov: 30)
• Consequence: PLOD2 NM_182943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902

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]

PLOD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLOD2	NM_182943.3	c.338+3157A>G		intron_variant		ENST00000282903.10	NP_891988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLOD2	ENST00000282903.10	c.338+3157A>G		intron_variant		1	NM_182943.3	ENSP00000282903.5

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72298 AN: 151492 Hom.: 17395 Cov.: 30

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.477 AC: 72341 AN: 151608 Hom.: 17405 Cov.: 30 AF XY: 0.476 AC XY: 35223 AN XY: 74030

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.488

Alfa AF: 0.474 Hom.: 2102

Bravo AF: 0.481

Asia WGS AF: 0.484 AC: 1684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
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: rs2864793; hg19: chr3-145835742;