rs1558874

Variant names:

• chr9-129711337-T-G
• rs1558874
• NM_016307.4:c.260-7894T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016307.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRX2	NM_016307.4	MANE Select	c.260-7894T>G		intron	N/A	NP_057391.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRX2	ENST00000372469.6	TSL:1 MANE Select	c.260-7894T>G		intron	N/A	ENSP00000361547.4

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

African (AFR) AF: 0.261 AC: 10710 AN: 41040

American (AMR) AF: 0.136 AC: 2060 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 622 AN: 3462

East Asian (EAS) AF: 0.339 AC: 1740 AN: 5140

South Asian (SAS) AF: 0.181 AC: 870 AN: 4814

European-Finnish (FIN) AF: 0.0896 AC: 934 AN: 10422

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8175 AN: 67870

Other (OTH) AF: 0.162 AC: 339 AN: 2098

Alfa AF: 0.136 Hom.: 880

Bravo AF: 0.178

Asia WGS AF: 0.234 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.35
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1558874; hg19: chr9-132473616;