Variant 2-1634339-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012293.3(PXDN):c.4321-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,562,008 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 22 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 19 hom. )

Consequence

PXDN
NM_012293.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.217

Variant links:

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]

PXDN links:

LOC124907723 (HGNC:):

LOC124907723 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-1634339-G-A is Benign according to our data. Variant chr2-1634339-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1216923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00974 (1484/152354) while in subpopulation AFR AF= 0.0344 (1429/41592). AF 95% confidence interval is 0.0329. There are 22 homozygotes in gnomad4. There are 688 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3 linkuse as main transcript	c.4321-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000252804.9	NP_036425.1
LOC124907723	XR_007086188.1 linkuse as main transcript	n.309G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9 linkuse as main transcript	c.4321-16C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_012293.3	ENSP00000252804	P1	Q92626-1
PXDN	ENST00000453308.1 linkuse as main transcript	c.*111-16C>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	3		ENSP00000414098
PXDN	ENST00000478155.5 linkuse as main transcript	n.3409-16C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2
PXDN	ENST00000493654.1 linkuse as main transcript	n.1658-16C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00975

AC:

1484

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00235

AC:

389

AN:

165398

Hom.:

AF XY:

0.00168

AC XY:

148

AN XY:

88152

show subpopulations

Gnomad AFR exome

AF:

0.0356

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000756

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000936

AC:

1319

AN:

1409654

Hom.:

Cov.:

AF XY:

0.000740

AC XY:

515

AN XY:

696220

show subpopulations

Gnomad4 AFR exome

AF:

0.0334

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000350

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00974

AC:

1484

AN:

152354

Hom.:

Cov.:

AF XY:

0.00924

AC XY:

688

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0344

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00517

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2018	- -

Anterior segment dysgenesis 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.74

DANN

Benign

0.50

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