chr1-17072019-C-A

Variant names:

• chr1-17072019-C-A
• rs910232
• NM_007365.3:c.1550-528G>T

Variant summary

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

The NM_007365.3(PADI2):​c.1550-528G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,004 control chromosomes in the GnomAD database, including 27,859 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 0.60 (27859 hom., cov: 32)
• Consequence: PADI2 NM_007365.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI2	NM_007365.3	MANE Select	c.1550-528G>T		intron	N/A	NP_031391.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI2	ENST00000375486.9	TSL:1 MANE Select	c.1550-528G>T		intron	N/A	ENSP00000364635.4
	PADI2	ENST00000466151.1	TSL:2	n.1906-528G>T		intron	N/A
	PADI2	ENST00000479534.5	TSL:2	n.497-528G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91333 AN: 151886 Hom.: 27853 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.609

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.601 AC: 91375 AN: 152004 Hom.: 27859 Cov.: 32 AF XY: 0.595 AC XY: 44212 AN XY: 74264

African (AFR) AF: 0.536 AC: 22221 AN: 41444

American (AMR) AF: 0.589 AC: 9006 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2314 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2033 AN: 5146

South Asian (SAS) AF: 0.561 AC: 2709 AN: 4826

European-Finnish (FIN) AF: 0.596 AC: 6300 AN: 10570

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44685 AN: 67950

Other (OTH) AF: 0.604 AC: 1276 AN: 2112

Alfa AF: 0.573 Hom.: 2967

Bravo AF: 0.598

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.66
PhyloP100		-1.4
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: rs910232; hg19: chr1-17398514;