3-146117955-T-C

Variant names:

• chr3-146117955-T-C
• rs2864793
• NM_182943.3:c.338+3157A>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.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
• Publications: 0 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=-0.91).
• 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 rank	MANE	Protein	UniProt
PLOD2	NM_182943.3	c.338+3157A>G		intron_variant	Intron 3 of 19	ENST00000282903.10	NP_891988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD2	ENST00000282903.10	c.338+3157A>G		intron_variant	Intron 3 of 19	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

African (AFR) AF: 0.506 AC: 20910 AN: 41328

American (AMR) AF: 0.463 AC: 7036 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1989 AN: 3464

East Asian (EAS) AF: 0.562 AC: 2869 AN: 5106

South Asian (SAS) AF: 0.435 AC: 2091 AN: 4804

European-Finnish (FIN) AF: 0.416 AC: 4371 AN: 10496

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31491 AN: 67892

Other (OTH) AF: 0.488 AC: 1027 AN: 2106

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
PhyloP100		-0.90
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: rs2864793; hg19: chr3-145835742;