rs1449444

Positions:

• chr3-146073016-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182943.3(PLOD2):​c.1743+271C>A 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 151,308 control chromosomes in the GnomAD database, including 17,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (17336 hom., cov: 32)
• Consequence: PLOD2 NM_182943.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.347

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-146073016-G-T is Benign according to our data. Variant chr3-146073016-G-T is described in ClinVar as [Benign]. Clinvar id is 1262573.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	UniProt
PLOD2	NM_182943.3	c.1743+271C>A		intron_variant		ENST00000282903.10
PLOD2	NM_000935.3	c.1680+271C>A		intron_variant
PLOD2	XM_017006625.3	c.1467+271C>A		intron_variant
PLOD2	XM_047448319.1	c.1467+271C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLOD2	ENST00000282903.10	c.1743+271C>A		intron_variant		1	NM_182943.3	P3
	ENST00000480247.1	n.337+4838G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72099 AN: 151190 Hom.: 17329 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.477 AC: 72138 AN: 151308 Hom.: 17336 Cov.: 32 AF XY: 0.475 AC XY: 35133 AN XY: 73912

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.486

Alfa AF: 0.474 Hom.: 23825

Bravo AF: 0.481

Asia WGS AF: 0.483 AC: 1677 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.61

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: rs1449444; hg19: chr3-145790803;