Genetic Variant NM_018192.4:c.*204_*211dupCTCTCTCT (chr3-189957700-A-AAGAGAGAG) – 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.*204_*211dupCTCTCTCT 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 0.25 ( 5440 hom., cov: 0)

Exomes 𝑓: 0.23 ( 844 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-AAGAGAGAG is Benign according to our data. Variant chr3-189957700-A-AAGAGAGAG is described in ClinVar as [Benign]. Clinvar id is 1267579.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4 link	c.204_211dupCTCTCTCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2	Q8IVL5-1
P3H2	NM_001134418.2 link	c.204_211dupCTCTCTCT		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.204_211dupCTCTCTCT	3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5	Q8IVL5-1
P3H2	ENST00000427335.6 link	c.204_211dupCTCTCTCT	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2	Q8IVL5-2
P3H2	ENST00000490940.1 link	n.461_468dupCTCTCTCT	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

37382

AN:

147214

Hom.:

5445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0882

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.273

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.232

AC:

90448

AN:

390292

Hom.:

844

Cov.:

AF XY:

0.234

AC XY:

49042

AN XY:

209564

show subpopulations

African (AFR)

AF:

0.0782

AC:

871

AN:

11132

American (AMR)

AF:

0.206

AC:

3442

AN:

16718

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

2048

AN:

11604

East Asian (EAS)

AF:

0.105

AC:

2705

AN:

25792

South Asian (SAS)

AF:

0.254

AC:

10811

AN:

42540

European-Finnish (FIN)

AF:

0.311

AC:

7200

AN:

23158

Middle Eastern (MID)

AF:

0.230

AC:

385

AN:

1674

European-Non Finnish (NFE)

AF:

0.246

AC:

58030

AN:

235592

Other (OTH)

AF:

0.224

AC:

4956

AN:

22082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

3638

7276

10914

14552

18190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.254

AC:

37381

AN:

147324

Hom.:

5440

Cov.:

AF XY:

0.257

AC XY:

18406

AN XY:

71538

show subpopulations

African (AFR)

AF:

0.0881

AC:

3535

AN:

40116

American (AMR)

AF:

0.280

AC:

4123

AN:

14710

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

770

AN:

3408

East Asian (EAS)

AF:

0.147

AC:

727

AN:

4952

South Asian (SAS)

AF:

0.317

AC:

1434

AN:

4522

European-Finnish (FIN)

AF:

0.419

AC:

4077

AN:

9732

Middle Eastern (MID)

AF:

0.262

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.327

AC:

21810

AN:

66704

Other (OTH)

AF:

0.260

AC:

529

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1172

2343

3515

4686

5858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.216

Hom.:

390

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 31, 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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NM_018192.4:c.204_211dupCTCTCTCT

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