NM_007365.3:c.92+1006C>A

Variant names:

• chr1-17118274-G-T
• rs1005753
• NM_007365.3:c.92+1006C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.0480
• Publications: 24 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007365.3. 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
	PADI2	NM_007365.3	MANE Select	c.92+1006C>A		intron	N/A	NP_031391.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI2	ENST00000375486.9	TSL:1 MANE Select	c.92+1006C>A		intron	N/A	ENSP00000364635.4
	PADI2	ENST00000375481.1	TSL:1	c.92+1006C>A		intron	N/A	ENSP00000364630.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84412 AN: 151768 Hom.: 25062 Cov.: 31

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.: 31 AF XY: 0.562 AC XY: 41758 AN XY: 74252

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		0.048
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: rs1005753; hg19: chr1-17444769; COSMIC: COSV64945569;