Variant 9-129719395-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016307.4(PRRX2):c.424A>G(p.Asn142Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000718 in 1,392,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

PRRX2
NM_016307.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

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]

PRRX2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX2	NM_016307.4 linkuse as main transcript	c.424A>G	p.Asn142Asp	missense_variant	2/4	ENST00000372469.6	NP_057391.1	Q99811A0A140VJS2
PRRX2	XM_017014803.1 linkuse as main transcript	c.244A>G	p.Asn82Asp	missense_variant	2/4		XP_016870292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRX2	ENST00000372469.6 linkuse as main transcript	c.424A>G	p.Asn142Asp	missense_variant	2/4	1	NM_016307.4	ENSP00000361547.4		Q99811

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000672

AC:

AN:

148710

Hom.:

AF XY:

0.00

AC XY:

AN XY:

80010

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:

0.0000802

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000718

AC:

AN:

1392852

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

686746

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:

0.00

Gnomad4 FIN exome

AF:

0.0000656

Gnomad4 NFE exome

AF:

0.00000650

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000476

Hom.:

ExAC

AF:

0.00000915

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

Jan 23, 2023

The c.424A>G (p.N142D) alteration is located in exon 2 (coding exon 2) of the PRRX2 gene. This alteration results from a A to G substitution at nucleotide position 424, causing the asparagine (N) at amino acid position 142 to be replaced by an aspartic acid (D). 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.095

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.51

MetaSVM

Uncertain

0.026

MutationAssessor

Benign

0.68

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.41

Sift

Benign

0.46

Sift4G

Benign

0.58

Polyphen

0.14

Vest4

0.57

MutPred

0.33

Loss of MoRF binding (P = 0.0497);

MVP

0.95

MPC

0.99

ClinPred

0.82

GERP RS

4.0

Varity_R

0.39

gMVP

0.86

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.

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