chr3-189957700-A-AAGAGAG

Variant names:

• chr3-189957700-A-AAGAGAG
• rs3062112
• NM_018192.4:c.*206_*211dupCTCTCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_018192.4(P3H2):​c.*206_*211dupCTCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.046 (0 hom.)
• Consequence: P3H2 NM_018192.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 3-189957700-A-AAGAGAG is Benign according to our data. Variant chr3-189957700-A-AAGAGAG is described in ClinVar as Likely_benign. ClinVar VariationId is 1220167.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*206_*211dupCTCTCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*206_*211dupCTCTCT		3_prime_UTR_variant	Exon 15 of 15		NP_001127890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H2	ENST00000319332.10	c.*206_*211dupCTCTCT		3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335.6	c.*206_*211dupCTCTCT		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2
P3H2	ENST00000490940.1	n.463_468dupCTCTCT		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.000984 AC: 145 AN: 147284 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000849

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.000543

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00694

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000479

Gnomad OTH AF: 0.000992

GnomAD4 exome AF: 0.0463 AC: 17936 AN: 387722 Hom.: 0 Cov.: 0 AF XY: 0.0466 AC XY: 9699 AN XY: 208308

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00832 AC: 93 AN: 11178

American (AMR) AF: 0.0385 AC: 644 AN: 16724

Ashkenazi Jewish (ASJ) AF: 0.0298 AC: 346 AN: 11592

East Asian (EAS) AF: 0.0156 AC: 404 AN: 25872

South Asian (SAS) AF: 0.0477 AC: 2014 AN: 42194

European-Finnish (FIN) AF: 0.0736 AC: 1676 AN: 22764

Middle Eastern (MID) AF: 0.0513 AC: 85 AN: 1658

European-Non Finnish (NFE) AF: 0.0499 AC: 11668 AN: 233710

Other (OTH) AF: 0.0457 AC: 1006 AN: 22030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000997 AC: 147 AN: 147394 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 77 AN XY: 71574

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000872 AC: 35 AN: 40150

American (AMR) AF: 0.000543 AC: 8 AN: 14742

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 4958

South Asian (SAS) AF: 0.000220 AC: 1 AN: 4536

European-Finnish (FIN) AF: 0.00694 AC: 67 AN: 9656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000479 AC: 32 AN: 66756

Other (OTH) AF: 0.000982 AC: 2 AN: 2036

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 390

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 24, 2019

GeneDx

Significance: Likely 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

Splicing

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

Other links and lift over

dbSNP: rs3062112; hg19: chr3-189675489; COSMIC: COSV60019318;