NM_007365.3:c.1881C>T

Variant names:

• chr1-17069161-G-A
• rs77285572
• NM_007365.3:c.1881C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI2	NM_007365.3	c.1881C>T	p.Leu627Leu	synonymous_variant	Exon 16 of 16	ENST00000375486.9	NP_031391.2
PADI2	XM_017000148.3	c.936C>T	p.Leu312Leu	synonymous_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.1881C>T	p.Leu627Leu	synonymous_variant	Exon 16 of 16	1	NM_007365.3	ENSP00000364635.4
PADI2	ENST00000466151.1	n.2237C>T		non_coding_transcript_exon_variant	Exon 7 of 7	2
PADI2	ENST00000479534.5	n.828C>T		non_coding_transcript_exon_variant	Exon 4 of 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

GnomAD2 exomes AF: 0.00286 AC: 720 AN: 251458 AF XY: 0.00215

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 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

African (AFR) AF: 0.0253 AC: 847 AN: 33480

American (AMR) AF: 0.00268 AC: 120 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 322 AN: 26136

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.000162 AC: 180 AN: 1111992

Other (OTH) AF: 0.00331 AC: 200 AN: 60396

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

African (AFR) AF: 0.0265 AC: 1102 AN: 41578

American (AMR) AF: 0.00771 AC: 118 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68032

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00977 Hom.: 15

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.1
DANN	Benign	0.69
PhyloP100		0.46
Mutation Taster		=98/2	polymorphism

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: rs77285572; hg19: chr1-17395656;