chr2-1635350-T-C

Position:

• chr2-1635350-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012293.3(PXDN):​c.4320+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,449,746 control chromosomes in the GnomAD database, including 50,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5393 hom., cov: 33)
  • Exomes 𝑓: 0.26 (44741 hom.)
• Consequence: PXDN NM_012293.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.872

Genes affected

PXDN (HGNC:14966): (peroxidasin) This gene encodes a heme-containing peroxidase that is secreted into the extracellular matrix. It is involved in extracellular matrix formation, and may function in the physiological and pathological fibrogenic response in fibrotic kidney. Mutations in this gene cause corneal opacification and other ocular anomalies, and also microphthalmia and anterior segment dysgenesis. [provided by RefSeq, Aug 2014]

LOC124907723 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-1635350-T-C is Benign according to our data. Variant chr2-1635350-T-C is described in ClinVar as [Benign]. Clinvar id is 1242594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3	c.4320+58A>G		intron_variant		ENST00000252804.9	NP_036425.1
LOC124907723	XR_007086188.1	n.344-335T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9	c.4320+58A>G		intron_variant		1	NM_012293.3	ENSP00000252804	P1
PXDN	ENST00000453308.1	c.*110+58A>G		intron_variant, NMD_transcript_variant		3		ENSP00000414098
PXDN	ENST00000478155.5	n.3408+58A>G		intron_variant, non_coding_transcript_variant		2
PXDN	ENST00000493654.1	n.1657+58A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39431 AN: 152060 Hom.: 5376 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.256 AC: 332527 AN: 1297568 Hom.: 44741 AF XY: 0.259 AC XY: 167224 AN XY: 645412

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.259 AC: 39485 AN: 152178 Hom.: 5393 Cov.: 33 AF XY: 0.266 AC XY: 19802 AN XY: 74388

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.254

Alfa AF: 0.223 Hom.: 1945

Bravo AF: 0.267

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.47

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: rs2241457; hg19: chr2-1639122; COSMIC: COSV53249460;