dbSNP rs1512900: PLOD2:c.110-10713C>G (chr3-146134942-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_182943.3(PLOD2):c.110-10713C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,078 control chromosomes in the GnomAD database, including 20,119 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 0.51 ( 20119 hom., cov: 33)

Consequence

PLOD2
NM_182943.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.762

Publications

2 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:

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=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLOD2	NM_182943.3 link	c.110-10713C>G	intron_variant	Intron 1 of 19	ENST00000282903.10	NP_891988.1	O00469-2
PLOD2	NM_000935.3 link	c.110-10713C>G	intron_variant	Intron 1 of 18		NP_000926.2	O00469-1
PLOD2	XM_047448320.1 link	c.110-10713C>G	intron_variant	Intron 1 of 16		XP_047304276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD2	ENST00000282903.10 link	c.110-10713C>G		intron_variant	Intron 1 of 19	1	NM_182943.3	ENSP00000282903.5		O00469-2

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77857

AN:

151960

Hom.:

20092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.580

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.473

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.515

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

GnomAD4 genome

AF:

0.512

AC:

77932

AN:

152078

Hom.:

20119

Cov.:

AF XY:

0.512

AC XY:

38036

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.580

AC:

24086

AN:

41498

American (AMR)

AF:

0.469

AC:

7164

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

2012

AN:

3470

East Asian (EAS)

AF:

0.561

AC:

2891

AN:

5156

South Asian (SAS)

AF:

0.471

AC:

2267

AN:

4818

European-Finnish (FIN)

AF:

0.473

AC:

5003

AN:

10570

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.482

AC:

32727

AN:

67966

Other (OTH)

AF:

0.519

AC:

1096

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2001

4002

6004

8005

10006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.496

Hom.:

2279

Bravo

AF:

0.515

Asia WGS

AF:

0.527

AC:

1833

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.90

(source)

DANN

Benign

0.47

PhyloP100

-0.76

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over