Variant 5-132203830-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365677.2(P4HA2):c.1169A>G(p.Asp390Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

P4HA2
NM_001365677.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Variant links:

Genes affected

P4HA2 (HGNC:8547): (prolyl 4-hydroxylase subunit alpha 2) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

P4HA2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06910595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P4HA2	NM_001365677.2 linkuse as main transcript	c.1169A>G	p.Asp390Gly	missense_variant	10/15	ENST00000379104.7
P4HA2	NM_001017974.2 linkuse as main transcript	c.1169A>G	p.Asp390Gly	missense_variant	10/15	ENST00000360568.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HA2	ENST00000379104.7 linkuse as main transcript	c.1169A>G	p.Asp390Gly	missense_variant	10/15	1	NM_001365677.2	P4	O15460-1
P4HA2	ENST00000360568.8 linkuse as main transcript	c.1169A>G	p.Asp390Gly	missense_variant	10/15	1	NM_001017974.2	A1	O15460-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251358

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461234

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.1169A>G (p.D390G) alteration is located in exon 10 (coding exon 9) of the P4HA2 gene. This alteration results from a A to G substitution at nucleotide position 1169, causing the aspartic acid (D) at amino acid position 390 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.18

T;.;T;.;.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

.;.;.;.;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.069

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.39

N;N;N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Benign

0.098

Sift

Benign

0.39

T;T;T;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;B

Vest4

0.30

MutPred

0.39

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.58

MPC

0.30

ClinPred

0.13

GERP RS

4.5

Varity_R

0.13

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over