rs1558874

chr9-129711337-T-G

Variant summary

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

The NM_016307.4(PRRX2):c.260-7894T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,188 control chromosomes in the GnomAD database, including 2,700 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 0.17 (2700 hom., cov: 30)
• Consequence: PRRX2 NM_016307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.45

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRX2	NM_016307.4	c.260-7894T>G		intron_variant		ENST00000372469.6
PRRX2	XM_017014803.1	c.80-7894T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRX2	ENST00000372469.6	c.260-7894T>G		intron_variant		1	NM_016307.4	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25557 AN: 151070 Hom.: 2692 Cov.: 30

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.169 AC: 25599 AN: 151188 Hom.: 2700 Cov.: 30 AF XY: 0.167 AC XY: 12320 AN XY: 73844

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0896

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.162

Alfa AF: 0.137 Hom.: 810

Bravo AF: 0.178

Asia WGS AF: 0.234 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.11
Dann	Benign	0.35

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: rs1558874; hg19: chr9-132473616;