19-35800132-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021232.2(PRODH2):c.1289G>A(p.Arg430Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R430L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PRODH2
NM_021232.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.883

Publications

0 publications found

Variant links:

Genes affected

PRODH2 (HGNC:17325): (proline dehydrogenase 2) The protein encoded by this gene catalyzes the first step in the catabolism of trans-4-hydroxy-L-proline, an amino acid derivative obtained through food intake and collagen turnover. One of the downstream products of this catabolism is glyoxylate, which in people with disorders of glyoxalate metabolism can lead to an increase in oxalate levels and the formation of calcium-oxalate kidney stones. Therefore, this gene may serve as a therapeutic target against primary hyperoxalurias (PH). This gene is similar to proline dehydrogenase (oxidase) 1, a mitochondrial enzyme that catalyzes the first step in proline catabolism. [provided by RefSeq, Jan 2017]

PRODH2 Gene-Disease associations (from GenCC):

hydroxyprolinemia
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

PRODH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18570384).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021232.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRODH2	NM_021232.2	MANE Select	c.1289G>A	p.Arg430Gln	missense	Exon 10 of 10	NP_067055.2	Q9UF12
PRODH2	NM_001378292.1		c.1133G>A	p.Arg378Gln	missense	Exon 9 of 9	NP_001365221.1
PRODH2	NM_001378293.1		c.*66G>A		3_prime_UTR	Exon 9 of 9	NP_001365222.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRODH2	ENST00000653904.2	MANE Select	c.1289G>A	p.Arg430Gln	missense	Exon 10 of 10	ENSP00000499779.1	Q9UF12
PRODH2	ENST00000301175.7	TSL:1	c.1289G>A	p.Arg430Gln	missense	Exon 11 of 11	ENSP00000301175.4	Q9UF12
PRODH2	ENST00000881789.1		c.1406G>A	p.Arg469Gln	missense	Exon 12 of 12	ENSP00000551848.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000126

AC:

AN:

237794

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000936

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455860

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723666

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33374

American (AMR)

AF:

0.00

AC:

AN:

43968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25896

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39530

South Asian (SAS)

AF:

0.0000235

AC:

AN:

85084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1109152

Other (OTH)

AF:

0.00

AC:

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.052

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.84

M_CAP

Benign

0.0063

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

PhyloP100

0.88

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

REVEL

Benign

0.044

Sift

Benign

0.12

Sift4G

Benign

0.17

Polyphen

0.39

Vest4

0.11

MutPred

0.53

Loss of MoRF binding (P = 0.0286)

MVP

0.21

MPC

0.19

ClinPred

0.32

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.093

gMVP

0.31

Mutation Taster

=87/13

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over