chr1-17070118-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007365.3(PADI2):​c.1734C>G​(p.Asp578Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PADI2
NM_007365.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.103

Publications

0 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038954675).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PADI2NM_007365.3 linkc.1734C>G p.Asp578Glu missense_variant Exon 15 of 16 ENST00000375486.9 NP_031391.2 Q9Y2J8-1
PADI2XM_017000148.3 linkc.789C>G p.Asp263Glu missense_variant Exon 7 of 8 XP_016855637.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PADI2ENST00000375486.9 linkc.1734C>G p.Asp578Glu missense_variant Exon 15 of 16 1 NM_007365.3 ENSP00000364635.4 Q9Y2J8-1
PADI2ENST00000466151.1 linkn.2090C>G non_coding_transcript_exon_variant Exon 6 of 7 2
PADI2ENST00000479534.5 linkn.681C>G non_coding_transcript_exon_variant Exon 3 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461812
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727224
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111970
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
2.0
DANN
Benign
0.23
DEOGEN2
Benign
0.018
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.064
N
LIST_S2
Benign
0.12
T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.26
N
PhyloP100
-0.10
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.32
N
REVEL
Benign
0.036
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.092
MutPred
0.26
Loss of ubiquitination at K574 (P = 0.1453);
MVP
0.11
MPC
0.18
ClinPred
0.052
T
GERP RS
0.28
Varity_R
0.19
gMVP
0.53
Mutation Taster
=86/14
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

Publications

Other links and lift over

dbSNP: rs2078254637; hg19: chr1-17396613; API