NM_182943.3:c.615+419A>G

Variant names:

• chr3-146106113-T-C
• rs9852153
• NM_182943.3:c.615+419A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Bruck syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Bruck syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLOD2	NM_182943.3	c.615+419A>G		intron_variant	Intron 5 of 19	ENST00000282903.10	NP_891988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD2	ENST00000282903.10	c.615+419A>G		intron_variant	Intron 5 of 19	1	NM_182943.3	ENSP00000282903.5

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

African (AFR) AF: 0.510 AC: 21169 AN: 41496

American (AMR) AF: 0.448 AC: 6848 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2916 AN: 5182

South Asian (SAS) AF: 0.434 AC: 2094 AN: 4824

European-Finnish (FIN) AF: 0.407 AC: 4305 AN: 10570

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30193 AN: 67976

Other (OTH) AF: 0.475 AC: 1003 AN: 2110

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
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9852153; hg19: chr3-145823900;