rs761426

Variant names:

• chr1-17087404-T-A
• rs761426
• NM_007365.3:c.656-705A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 = 0.573 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI2	NM_007365.3	MANE Select	c.656-705A>T		intron	N/A	NP_031391.2	Q9Y2J8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI2	ENST00000375486.9	TSL:1 MANE Select	c.656-705A>T		intron	N/A	ENSP00000364635.4	Q9Y2J8-1
	PADI2	ENST00000375481.1	TSL:1	c.656-705A>T		intron	N/A	ENSP00000364630.1	Q9Y2J8-2
	PADI2	ENST00000908716.1		c.722-705A>T		intron	N/A	ENSP00000578775.1

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

African (AFR) AF: 0.365 AC: 15135 AN: 41446

American (AMR) AF: 0.349 AC: 5339 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3057 AN: 5178

South Asian (SAS) AF: 0.430 AC: 2075 AN: 4820

European-Finnish (FIN) AF: 0.374 AC: 3949 AN: 10556

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18500 AN: 67970

Other (OTH) AF: 0.323 AC: 682 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		0.023
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: rs761426; hg19: chr1-17413899; COSMIC: COSV64945540; COSMIC: COSV64945540;