rs1449444

Variant names:

• chr3-146073016-G-T
• rs1449444
• NM_182943.3:c.1743+271C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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

ENSG00000243415 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PLOD2	NM_182943.3	c.1743+271C>A		intron_variant	Intron 16 of 19	ENST00000282903.10	NP_891988.1
PLOD2	NM_000935.3	c.1680+271C>A		intron_variant	Intron 15 of 18		NP_000926.2
PLOD2	XM_017006625.3	c.1467+271C>A		intron_variant	Intron 17 of 20		XP_016862114.1
PLOD2	XM_047448319.1	c.1467+271C>A		intron_variant	Intron 16 of 19		XP_047304275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD2	ENST00000282903.10	c.1743+271C>A		intron_variant	Intron 16 of 19	1	NM_182943.3	ENSP00000282903.5

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

African (AFR) AF: 0.504 AC: 20857 AN: 41398

American (AMR) AF: 0.463 AC: 6997 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1984 AN: 3456

East Asian (EAS) AF: 0.564 AC: 2899 AN: 5138

South Asian (SAS) AF: 0.436 AC: 2105 AN: 4824

European-Finnish (FIN) AF: 0.417 AC: 4394 AN: 10538

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

European-Non Finnish (NFE) AF: 0.464 AC: 31325 AN: 67528

Other (OTH) AF: 0.486 AC: 1020 AN: 2098

Alfa AF: 0.473 Hom.: 34918

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

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.61
PhyloP100		-0.35
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: rs1449444; hg19: chr3-145790803;