3-146117596-A-G

Variant names:

• chr3-146117596-A-G
• rs12496198
• NM_182943.3:c.338+3516T>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+3516T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,834 control chromosomes in the GnomAD database, including 15,076 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 0.44 (15076 hom., cov: 31)
• Consequence: PLOD2 NM_182943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLOD2	NM_182943.3	c.338+3516T>C		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+3516T>C		intron_variant	Intron 3 of 19	1	NM_182943.3	ENSP00000282903.5

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67348 AN: 151714 Hom.: 15076 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.444 AC: 67373 AN: 151834 Hom.: 15076 Cov.: 31 AF XY: 0.442 AC XY: 32807 AN XY: 74192

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.463

Alfa AF: 0.448 Hom.: 4252

Bravo AF: 0.448

Asia WGS AF: 0.475 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.38

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: rs12496198; hg19: chr3-145835383;