chr1-17068786-T-C

Variant names:

• chr1-17068786-T-C
• rs2235926
• NM_007365.3:c.*258A>G

Variant summary

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

The NM_007365.3(PADI2):​c.*258A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 527,180 control chromosomes in the GnomAD database, including 29,908 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 (8468 hom., cov: 32)
  • Exomes 𝑓: 0.33 (21440 hom.)
• Consequence: PADI2 NM_007365.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 18 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 = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI2	NM_007365.3	c.*258A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000375486.9	NP_031391.2
PADI2	XM_017000148.3	c.*258A>G		3_prime_UTR_variant	Exon 8 of 8		XP_016855637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI2	ENST00000375486.9	c.*258A>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_007365.3	ENSP00000364635.4
PADI2	ENST00000466151.1	n.2612A>G		non_coding_transcript_exon_variant	Exon 7 of 7	2
PADI2	ENST00000479534.5	n.1203A>G		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49536 AN: 151926 Hom.: 8447 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.326 AC: 122408 AN: 375136 Hom.: 21440 Cov.: 0 AF XY: 0.330 AC XY: 64946 AN XY: 196538

African (AFR) AF: 0.330 AC: 3631 AN: 10998

American (AMR) AF: 0.347 AC: 5389 AN: 15508

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 3046 AN: 11710

East Asian (EAS) AF: 0.570 AC: 14302 AN: 25092

South Asian (SAS) AF: 0.407 AC: 16304 AN: 40012

European-Finnish (FIN) AF: 0.327 AC: 7666 AN: 23468

Middle Eastern (MID) AF: 0.240 AC: 395 AN: 1646

European-Non Finnish (NFE) AF: 0.288 AC: 64745 AN: 224922

Other (OTH) AF: 0.318 AC: 6930 AN: 21780

GnomAD4 genome AF: 0.326 AC: 49602 AN: 152044 Hom.: 8468 Cov.: 32 AF XY: 0.333 AC XY: 24782 AN XY: 74312

African (AFR) AF: 0.323 AC: 13403 AN: 41460

American (AMR) AF: 0.366 AC: 5588 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3468

East Asian (EAS) AF: 0.598 AC: 3081 AN: 5154

South Asian (SAS) AF: 0.428 AC: 2062 AN: 4816

European-Finnish (FIN) AF: 0.349 AC: 3695 AN: 10580

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19825 AN: 67962

Other (OTH) AF: 0.326 AC: 689 AN: 2116

Alfa AF: 0.302 Hom.: 8980

Bravo AF: 0.324

Asia WGS AF: 0.504 AC: 1752 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	3.5
DANN	Benign	0.66
PhyloP100		-0.28
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: rs2235926; hg19: chr1-17395281;