NM_182943.3:c.110-10713C>G

Variant names:

• chr3-146134942-G-C
• rs1512900
• NM_182943.3:c.110-10713C>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.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
• Publications: 2 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=-0.99).
• 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 rank	MANE	Protein	UniProt
PLOD2	NM_182943.3	c.110-10713C>G		intron_variant	Intron 1 of 19	ENST00000282903.10	NP_891988.1
PLOD2	NM_000935.3	c.110-10713C>G		intron_variant	Intron 1 of 18		NP_000926.2
PLOD2	XM_047448320.1	c.110-10713C>G		intron_variant	Intron 1 of 16		XP_047304276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD2	ENST00000282903.10	c.110-10713C>G		intron_variant	Intron 1 of 19	1	NM_182943.3	ENSP00000282903.5

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

African (AFR) AF: 0.580 AC: 24086 AN: 41498

American (AMR) AF: 0.469 AC: 7164 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.561 AC: 2891 AN: 5156

South Asian (SAS) AF: 0.471 AC: 2267 AN: 4818

European-Finnish (FIN) AF: 0.473 AC: 5003 AN: 10570

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32727 AN: 67966

Other (OTH) AF: 0.519 AC: 1096 AN: 2112

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
PhyloP100		-0.76
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: rs1512900; hg19: chr3-145852729;