Genetic Variant PADI2:c.92+1006C>A (chr1-17118274-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007365.3(PADI2):c.92+1006C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,888 control chromosomes in the GnomAD database, including 25,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.56 ( 25077 hom., cov: 31)

Consequence

PADI2
NM_007365.3 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.0480

Publications

24 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI2	NM_007365.3 link	c.92+1006C>A		intron_variant	Intron 1 of 15	ENST00000375486.9	NP_031391.2
PADI2	XM_047442975.1 link	c.92+1006C>A		intron_variant	Intron 1 of 10		XP_047298931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI2	ENST00000375486.9 link	c.92+1006C>A		intron_variant	Intron 1 of 15	1	NM_007365.3	ENSP00000364635.4
PADI2	ENST00000375481.1 link	c.92+1006C>A		intron_variant	Intron 1 of 10	1		ENSP00000364630.1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84412

AN:

151768

Hom.:

25062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.871

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.680

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.568

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

GnomAD4 genome

AF:

0.556

AC:

84450

AN:

151888

Hom.:

25077

Cov.:

AF XY:

0.562

AC XY:

41758

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.347

AC:

14359

AN:

41406

American (AMR)

AF:

0.624

AC:

9527

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1626

AN:

3470

East Asian (EAS)

AF:

0.871

AC:

4485

AN:

5148

South Asian (SAS)

AF:

0.729

AC:

3503

AN:

4808

European-Finnish (FIN)

AF:

0.680

AC:

7186

AN:

10566

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.616

AC:

41835

AN:

67910

Other (OTH)

AF:

0.569

AC:

1199

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1759

3518

5278

7037

8796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.591

Hom.:

118504

Bravo

AF:

0.539

Asia WGS

AF:

0.730

AC:

2536

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Rheumatoid arthritis;C5441745:Abnormal pulmonary interstitial morphology

Other:1

Feb 01, 2020

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:association

Review Status:no assertion criteria provided

Collection Method:case-control

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.2

(source)

DANN

Benign

0.47

PhyloP100

0.048

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over