Genetic Variant P3H2:c.*210_*211dupCT (chr3-189957700-A-AAG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_018192.4(P3H2):c.*210_*211dupCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.074 ( 1040 hom., cov: 0)

Exomes 𝑓: 0.033 ( 45 hom. )

Consequence

P3H2
NM_018192.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.38

Publications

0 publications found

Variant links:

Genes affected

P3H2 (HGNC:19317): (prolyl 3-hydroxylase 2) This gene encodes a member of the prolyl 3-hydroxylase subfamily of 2-oxo-glutarate-dependent dioxygenases. These enzymes play a critical role in collagen chain assembly, stability and cross-linking by catalyzing post-translational 3-hydroxylation of proline residues. Mutations in this gene are associated with nonsyndromic severe myopia with cataract and vitreoretinal degeneration, and downregulation of this gene may play a role in breast cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

P3H2 Gene-Disease associations (from GenCC):

myopia, high, with cataract and vitreoretinal degeneration
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics

P3H2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 3-189957700-A-AAG is Benign according to our data. Variant chr3-189957700-A-AAG is described in ClinVar as [Benign]. Clinvar id is 1280894.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4 link	c.210_211dupCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2	Q8IVL5-1
P3H2	NM_001134418.2 link	c.210_211dupCT		3_prime_UTR_variant	Exon 15 of 15		NP_001127890.1	Q8IVL5-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
P3H2	ENST00000319332.10 link	c.210_211dupCT	3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5	Q8IVL5-1
P3H2	ENST00000427335.6 link	c.210_211dupCT	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2	Q8IVL5-2
P3H2	ENST00000490940.1 link	n.467_468dupCT	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0742

AC:

10943

AN:

147398

Hom.:

1041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.00116

Gnomad AMR

AF:

0.0597

Gnomad ASJ

AF:

0.0111

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.0454

Gnomad FIN

AF:

0.000716

Gnomad MID

AF:

0.0195

Gnomad NFE

AF:

0.00515

Gnomad OTH

AF:

0.0530

GnomAD4 exome

AF:

0.0335

AC:

13203

AN:

394628

Hom.:

Cov.:

AF XY:

0.0327

AC XY:

6928

AN XY:

212060

show subpopulations

African (AFR)

AF:

0.168

AC:

1871

AN:

11154

American (AMR)

AF:

0.0629

AC:

1065

AN:

16938

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

149

AN:

11692

East Asian (EAS)

AF:

0.236

AC:

6089

AN:

25834

South Asian (SAS)

AF:

0.0401

AC:

1737

AN:

43352

European-Finnish (FIN)

AF:

0.00300

AC:

AN:

23370

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

1688

European-Non Finnish (NFE)

AF:

0.00567

AC:

1351

AN:

238284

Other (OTH)

AF:

0.0382

AC:

852

AN:

22316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

488

976

1463

1951

2439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0743

AC:

10965

AN:

147508

Hom.:

1040

Cov.:

AF XY:

0.0752

AC XY:

5386

AN XY:

71662

show subpopulations

African (AFR)

AF:

0.194

AC:

7789

AN:

40076

American (AMR)

AF:

0.0601

AC:

887

AN:

14748

Ashkenazi Jewish (ASJ)

AF:

0.0111

AC:

AN:

3416

East Asian (EAS)

AF:

0.319

AC:

1579

AN:

4954

South Asian (SAS)

AF:

0.0455

AC:

206

AN:

4532

European-Finnish (FIN)

AF:

0.000716

AC:

AN:

9778

Middle Eastern (MID)

AF:

0.0245

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00513

AC:

343

AN:

66818

Other (OTH)

AF:

0.0529

AC:

108

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

424

848

1272

1696

2120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00143

Hom.:

390

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 26, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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3-189957700-A-AAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over