9-129665931-C-G

Variant summary

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

The NM_016307.4(PRRX2):ā€‹c.64C>Gā€‹(p.Pro22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 1,121,662 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 (ā˜…).

Frequency

Genomes: š‘“ 0.00028 ( 0 hom., cov: 31)
Exomes š‘“: 0.00053 ( 0 hom. )

Consequence

PRRX2
NM_016307.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0750
Variant links:
Genes affected
PRRX2 (HGNC:21338): (paired related homeobox 2) The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins. Expression is localized to proliferating fetal fibroblasts and the developing dermal layer, with downregulated expression in adult skin. Increases in expression of this gene during fetal but not adult wound healing suggest a possible role in mechanisms that control mammalian dermal regeneration and prevent formation of scar response to wounding. The expression patterns provide evidence consistent with a role in fetal skin development and a possible role in cellular proliferation. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.12904048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRRX2NM_016307.4 linkc.64C>G p.Pro22Ala missense_variant 1/4 ENST00000372469.6 NP_057391.1 Q99811A0A140VJS2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRRX2ENST00000372469.6 linkc.64C>G p.Pro22Ala missense_variant 1/41 NM_016307.4 ENSP00000361547.4 Q99811

Frequencies

GnomAD3 genomes
AF:
0.000285
AC:
42
AN:
147282
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000980
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000674
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000560
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000664
AC:
1
AN:
15066
Hom.:
0
AF XY:
0.000109
AC XY:
1
AN XY:
9186
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000193
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000533
AC:
519
AN:
974274
Hom.:
0
Cov.:
29
AF XY:
0.000496
AC XY:
234
AN XY:
471370
show subpopulations
Gnomad4 AFR exome
AF:
0.0000557
Gnomad4 AMR exome
AF:
0.000169
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000896
Gnomad4 NFE exome
AF:
0.000595
Gnomad4 OTH exome
AF:
0.000293
GnomAD4 genome
AF:
0.000285
AC:
42
AN:
147388
Hom.:
0
Cov.:
31
AF XY:
0.000320
AC XY:
23
AN XY:
71786
show subpopulations
Gnomad4 AFR
AF:
0.0000977
Gnomad4 AMR
AF:
0.0000673
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000560
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000529
Hom.:
0
Bravo
AF:
0.000242

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 submitterclinical testingAmbry GeneticsAug 02, 2021The c.64C>G (p.P22A) alteration is located in exon 1 (coding exon 1) of the PRRX2 gene. This alteration results from a C to G substitution at nucleotide position 64, causing the proline (P) at amino acid position 22 to be replaced by an alanine (A). 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
0.051
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
15
DANN
Benign
0.75
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.50
D
LIST_S2
Benign
0.45
T
M_CAP
Pathogenic
0.39
D
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.22
N
REVEL
Benign
0.18
Sift
Benign
0.16
T
Sift4G
Benign
1.0
T
Polyphen
0.060
B
Vest4
0.21
MutPred
0.27
Loss of glycosylation at P22 (P = 9e-04);
MVP
0.86
MPC
0.41
ClinPred
0.015
T
GERP RS
1.5
Varity_R
0.061
gMVP
0.29

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

LitVar

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

Other links and lift over

dbSNP: rs915395706; hg19: chr9-132428210; API