1-17069161-G-A

Position:

• chr1-17069161-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_007365.3(PADI2):​c.1881C>T​(p.Leu627Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,614,210 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (19 hom.)
• Consequence: PADI2 NM_007365.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.458

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]

PADI2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-17069161-G-A is Benign according to our data. Variant chr1-17069161-G-A is described in ClinVar as [Benign]. Clinvar id is 783278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.458 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00866 (1319/152336) while in subpopulation AFR AF= 0.0265 (1102/41578). AF 95% confidence interval is 0.0252. There are 13 homozygotes in gnomad4. There are 617 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI2	NM_007365.3	c.1881C>T	p.Leu627Leu	synonymous_variant	16/16	ENST00000375486.9	NP_031391.2
PADI2	XM_017000148.3	c.936C>T	p.Leu312Leu	synonymous_variant	8/8		XP_016855637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI2	ENST00000375486.9	c.1881C>T	p.Leu627Leu	synonymous_variant	16/16	1	NM_007365.3	ENSP00000364635.4
PADI2	ENST00000466151.1	n.2237C>T		non_coding_transcript_exon_variant	7/7	2
PADI2	ENST00000479534.5	n.828C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.00869 AC: 1323 AN: 152218 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00286 AC: 720 AN: 251458 Hom.: 11 AF XY: 0.00215 AC XY: 292 AN XY: 135910

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00116 AC: 1702 AN: 1461874 Hom.: 19 Cov.: 33 AF XY: 0.00104 AC XY: 753 AN XY: 727238

Gnomad4 AFR exome AF: 0.0253

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000162

Gnomad4 OTH exome AF: 0.00331

GnomAD4 genome AF: 0.00866 AC: 1319 AN: 152336 Hom.: 13 Cov.: 33 AF XY: 0.00828 AC XY: 617 AN XY: 74482

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00524 Hom.: 2

Bravo AF: 0.0105

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.1
DANN	Benign	0.69

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: rs77285572; hg19: chr1-17395656;