9-129681820-A-G

Position:

• chr9-129681820-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016307.4(PRRX2):​c.259+15694A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,066 control chromosomes in the GnomAD database, including 12,320 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (12320 hom., cov: 32)
• Consequence: PRRX2 NM_016307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX2	NM_016307.4	c.259+15694A>G		intron_variant		ENST00000372469.6	NP_057391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRX2	ENST00000372469.6	c.259+15694A>G		intron_variant		1	NM_016307.4	ENSP00000361547.4

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59460 AN: 151946 Hom.: 12300 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.391 AC: 59523 AN: 152066 Hom.: 12320 Cov.: 32 AF XY: 0.393 AC XY: 29223 AN XY: 74338

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.394

Alfa AF: 0.339 Hom.: 20025

Bravo AF: 0.396

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs7866070; hg19: chr9-132444099;