Variant 1-17075721-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_007365.3(PADI2):c.1413C>T(p.His471His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,614,014 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 27 hom. )

Consequence

PADI2
NM_007365.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.311

Variant links:

Genes affected

PADI2 (HGNC:18341): (peptidyl arginine deiminase 2) This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. The type II enzyme is the most widely expressed family member. Known substrates for this enzyme include myelin basic protein in the central nervous system and vimentin in skeletal muscle and macrophages. This enzyme is thought to play a role in the onset and progression of neurodegenerative human disorders, including Alzheimer disease and multiple sclerosis, and it has also been implicated in glaucoma pathogenesis. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]

PADI2 links:

PADI2 (HGNC:):

PADI2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 1-17075721-G-A is Benign according to our data. Variant chr1-17075721-G-A is described in ClinVar as [Benign]. Clinvar id is 773390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.311 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI2	NM_007365.3 linkuse as main transcript	c.1413C>T	p.His471His	synonymous_variant	12/16	ENST00000375486.9	NP_031391.2	Q9Y2J8-1
PADI2	XM_017000148.3 linkuse as main transcript	c.468C>T	p.His156His	synonymous_variant	4/8		XP_016855637.1
PADI2	XM_047442975.1 linkuse as main transcript	c.*67C>T		3_prime_UTR_variant	11/11		XP_047298931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI2	ENST00000375486.9 linkuse as main transcript	c.1413C>T	p.His471His	synonymous_variant	12/16	1	NM_007365.3	ENSP00000364635.4		Q9Y2J8-1
PADI2	ENST00000466151.1 linkuse as main transcript	n.1040C>T		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

532

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00619

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00324

AC:

814

AN:

251186

Hom.:

AF XY:

0.00334

AC XY:

453

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00340

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.00523

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00516

AC:

7537

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

3631

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00351

Gnomad4 FIN exome

AF:

0.00208

Gnomad4 NFE exome

AF:

0.00605

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.00350

AC:

533

AN:

152298

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00619

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00428

Hom.:

Bravo

AF:

0.00319

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00522

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.5

DANN

Benign

0.91

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