chr1-17075797-A-G

Position:

• chr1-17075797-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007365.3(PADI2):​c.1337T>C​(p.Val446Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PADI2 NM_007365.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.87

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2026254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI2	NM_007365.3	c.1337T>C	p.Val446Ala	missense_variant	12/16	ENST00000375486.9	NP_031391.2
PADI2	XM_017000148.3	c.392T>C	p.Val131Ala	missense_variant	4/8		XP_016855637.1
PADI2	XM_047442975.1	c.1185T>C	p.Gly395Gly	synonymous_variant	11/11		XP_047298931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI2	ENST00000375486.9	c.1337T>C	p.Val446Ala	missense_variant	12/16	1	NM_007365.3	ENSP00000364635.4
PADI2	ENST00000466151.1	n.964T>C		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.1337T>C (p.V446A) alteration is located in exon 12 (coding exon 12) of the PADI2 gene. This alteration results from a T to C substitution at nucleotide position 1337, causing the valine (V) at amino acid position 446 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.0062
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.68	T
Sift4G	Benign	0.99	T
Polyphen		0.29	B
Vest4		0.17
MutPred		0.66		Loss of methylation at K445 (P = 0.0475);
MVP		0.31
MPC		0.24
ClinPred		0.53	D
GERP RS		4.1
Varity_R		0.37
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-17402292;