rs2235927

Positions:

• chr1-17068280-G-A
• chr1-17068280-G-C
• chr1-17068280-G-T

Variant summary

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

The NM_007365.3(PADI2):​c.*764C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,598 control chromosomes in the GnomAD database, including 9,233 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 0.34 (9212 hom., cov: 33)
  • Exomes 𝑓: 0.32 (21 hom.)
• Consequence: PADI2 NM_007365.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI2	NM_007365.3	c.*764C>T		3_prime_UTR_variant	16/16	ENST00000375486.9	NP_031391.2
PADI2	XM_017000148.3	c.*764C>T		3_prime_UTR_variant	8/8		XP_016855637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI2	ENST00000375486.9	c.*764C>T		3_prime_UTR_variant	16/16	1	NM_007365.3	ENSP00000364635	P1
PADI2	ENST00000466151.1	n.3118C>T		non_coding_transcript_exon_variant	7/7	2
PADI2	ENST00000479534.5	n.1709C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51702 AN: 151992 Hom.: 9189 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.322 AC: 157 AN: 488 Hom.: 21 Cov.: 0 AF XY: 0.339 AC XY: 99 AN XY: 292

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.340 AC: 51773 AN: 152110 Hom.: 9212 Cov.: 33 AF XY: 0.347 AC XY: 25794 AN XY: 74348

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.333

Alfa AF: 0.297 Hom.: 9317

Bravo AF: 0.340

Asia WGS AF: 0.508 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.64

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: rs2235927; hg19: chr1-17394775; COSMIC: COSV64954398;