rs10788656

Variant names:

• chr1-17110835-G-C
• rs10788656
• NM_007365.3:c.93-5774C>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.93-5774C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,926 control chromosomes in the GnomAD database, including 29,976 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 0.61 (29976 hom., cov: 33)
• Consequence: PADI2 NM_007365.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI2	NM_007365.3	c.93-5774C>G		intron_variant	Intron 1 of 15	ENST00000375486.9	NP_031391.2
PADI2	XM_047442975.1	c.93-5774C>G		intron_variant	Intron 1 of 10		XP_047298931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI2	ENST00000375486.9	c.93-5774C>G		intron_variant	Intron 1 of 15	1	NM_007365.3	ENSP00000364635.4
PADI2	ENST00000375481.1	c.93-5774C>G		intron_variant	Intron 1 of 10	1		ENSP00000364630.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91985 AN: 151808 Hom.: 29966 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.606 AC: 92013 AN: 151926 Hom.: 29976 Cov.: 33 AF XY: 0.610 AC XY: 45285 AN XY: 74242

African (AFR) AF: 0.350 AC: 14458 AN: 41306

American (AMR) AF: 0.661 AC: 10099 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1904 AN: 3464

East Asian (EAS) AF: 0.871 AC: 4518 AN: 5186

South Asian (SAS) AF: 0.750 AC: 3614 AN: 4820

European-Finnish (FIN) AF: 0.735 AC: 7757 AN: 10560

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47547 AN: 67994

Other (OTH) AF: 0.608 AC: 1282 AN: 2108

Alfa AF: 0.647 Hom.: 4161

Bravo AF: 0.586

Asia WGS AF: 0.744 AC: 2587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.65
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: rs10788656; hg19: chr1-17437330; COSMIC: COSV64945558;