rs761426

Positions:

• chr1-17087404-T-A
• chr1-17087404-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007365.3(PADI2):​c.656-705A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,040 control chromosomes in the GnomAD database, including 8,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8668 hom., cov: 33)
• Consequence: PADI2 NM_007365.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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

Verdict is Benign. Variant got -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 = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI2	NM_007365.3	c.656-705A>T		intron_variant		ENST00000375486.9	NP_031391.2
PADI2	XM_047442975.1	c.656-705A>T		intron_variant			XP_047298931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI2	ENST00000375486.9	c.656-705A>T		intron_variant		1	NM_007365.3	ENSP00000364635.4
PADI2	ENST00000375481.1	c.656-705A>T		intron_variant		1		ENSP00000364630.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49885 AN: 151922 Hom.: 8654 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.328 AC: 49940 AN: 152040 Hom.: 8668 Cov.: 33 AF XY: 0.338 AC XY: 25082 AN XY: 74316

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.323

Alfa AF: 0.300 Hom.: 843

Bravo AF: 0.324

Asia WGS AF: 0.495 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.51

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: rs761426; hg19: chr1-17413899; COSMIC: COSV64945540; COSMIC: COSV64945540;