rs910232

Positions:

• chr1-17072019-C-A
• chr1-17072019-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI2	NM_007365.3	c.1550-528G>T		intron_variant		ENST00000375486.9
PADI2	XM_017000148.3	c.605-528G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI2	ENST00000375486.9	c.1550-528G>T		intron_variant		1	NM_007365.3	P1
PADI2	ENST00000466151.1	n.1906-528G>T		intron_variant, non_coding_transcript_variant		2
PADI2	ENST00000479534.5	n.497-528G>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.604

Alfa AF: 0.576 Hom.: 2858

Bravo AF: 0.598

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.66

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: rs910232; hg19: chr1-17398514;