Genetic Variant P3H2:c.*208_*211delCTCT (chr3-189957700-AAGAG-A) – 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.*208_*211delCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 536,322 control chromosomes in the GnomAD database, including 1,372 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.086 ( 1226 hom., cov: 0)

Exomes 𝑓: 0.034 ( 146 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-AAGAG-A is Benign according to our data. Variant chr3-189957700-AAGAG-A is described in ClinVar as [Benign]. Clinvar id is 1230099.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4 link	c.208_211delCTCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2	Q8IVL5-1
P3H2	NM_001134418.2 link	c.208_211delCTCT		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.208_211delCTCT	3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5	Q8IVL5-1
P3H2	ENST00000427335.6 link	c.208_211delCTCT	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2	Q8IVL5-2
P3H2	ENST00000490940.1 link	n.465_468delCTCT	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0857

AC:

12639

AN:

147408

Hom.:

1223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.0128

Gnomad AMR

AF:

0.0375

Gnomad ASJ

AF:

0.00410

Gnomad EAS

AF:

0.00885

Gnomad SAS

AF:

0.0293

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.0422

Gnomad NFE

AF:

0.0285

Gnomad OTH

AF:

0.0679

GnomAD4 exome

AF:

0.0337

AC:

13098

AN:

388802

Hom.:

146

AF XY:

0.0328

AC XY:

6850

AN XY:

208896

show subpopulations

African (AFR)

AF:

0.221

AC:

2454

AN:

11112

American (AMR)

AF:

0.0306

AC:

512

AN:

16710

Ashkenazi Jewish (ASJ)

AF:

0.00744

AC:

AN:

11430

East Asian (EAS)

AF:

0.0126

AC:

322

AN:

25604

South Asian (SAS)

AF:

0.0286

AC:

1223

AN:

42734

European-Finnish (FIN)

AF:

0.0220

AC:

507

AN:

23074

Middle Eastern (MID)

AF:

0.0401

AC:

AN:

1670

European-Non Finnish (NFE)

AF:

0.0300

AC:

7030

AN:

234466

Other (OTH)

AF:

0.0408

AC:

898

AN:

22002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

510

1020

1529

2039

2549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0859

AC:

12678

AN:

147520

Hom.:

1226

Cov.:

AF XY:

0.0830

AC XY:

5945

AN XY:

71656

show subpopulations

African (AFR)

AF:

0.241

AC:

9675

AN:

40092

American (AMR)

AF:

0.0375

AC:

553

AN:

14752

Ashkenazi Jewish (ASJ)

AF:

0.00410

AC:

AN:

3414

East Asian (EAS)

AF:

0.00887

AC:

AN:

4958

South Asian (SAS)

AF:

0.0291

AC:

132

AN:

4534

European-Finnish (FIN)

AF:

0.0202

AC:

197

AN:

9766

Middle Eastern (MID)

AF:

0.0350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0285

AC:

1905

AN:

66820

Other (OTH)

AF:

0.0672

AC:

137

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

481

961

1442

1922

2403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0158

Hom.:

390

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 13, 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

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

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3-189957700-AAGAG-A

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