dbSNP rs4681294: PLOD2:n.2407C>T (chr3-146077353-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000478436.1(PLOD2):n.2407C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 179,440 control chromosomes in the GnomAD database, including 19,439 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 0.46 ( 16437 hom., cov: 32)

Exomes 𝑓: 0.46 ( 3002 hom. )

Consequence

PLOD2
ENST00000478436.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.246

Publications

3 publications found

Variant links:

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

PLOD2 links:

ENSG00000243415 (HGNC:):

ENSG00000243415 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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 link	c.1564-458C>T		intron_variant	Intron 14 of 19	ENST00000282903.10	NP_891988.1	O00469-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD2	ENST00000282903.10 link	c.1564-458C>T		intron_variant	Intron 14 of 19	1	NM_182943.3	ENSP00000282903.5		O00469-2

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70275

AN:

151280

Hom.:

16431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.480

GnomAD4 exome

AF:

0.458

AC:

12852

AN:

28042

Hom.:

3002

Cov.:

AF XY:

0.463

AC XY:

6682

AN XY:

14428

show subpopulations

African (AFR)

AF:

0.505

AC:

214

AN:

424

American (AMR)

AF:

0.455

AC:

378

AN:

830

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

159

AN:

262

East Asian (EAS)

AF:

0.565

AC:

216

AN:

382

South Asian (SAS)

AF:

0.498

AC:

643

AN:

1290

European-Finnish (FIN)

AF:

0.426

AC:

144

AN:

338

Middle Eastern (MID)

AF:

0.650

AC:

AN:

European-Non Finnish (NFE)

AF:

0.450

AC:

10547

AN:

23424

Other (OTH)

AF:

0.496

AC:

512

AN:

1032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

344

688

1033

1377

1721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.464

AC:

70315

AN:

151398

Hom.:

16437

Cov.:

AF XY:

0.464

AC XY:

34336

AN XY:

73998

show subpopulations

African (AFR)

AF:

0.500

AC:

20695

AN:

41356

American (AMR)

AF:

0.448

AC:

6777

AN:

15140

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1951

AN:

3456

East Asian (EAS)

AF:

0.564

AC:

2900

AN:

5144

South Asian (SAS)

AF:

0.434

AC:

2096

AN:

4826

European-Finnish (FIN)

AF:

0.408

AC:

4295

AN:

10528

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.444

AC:

30057

AN:

67642

Other (OTH)

AF:

0.474

AC:

997

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1961

3923

5884

7846

9807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.455

Hom.:

2671

Bravo

AF:

0.468

Asia WGS

AF:

0.482

AC:

1678

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.26

(source)

DANN

Benign

0.42

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over