NM_007365.3:c.1655_1656delGTinsAC

Variant names:

• chr1-17070196-AC-GT
• NM_007365.3:c.1655_1656delGTinsAC
• PADI2 p.Arg552His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_007365.3(PADI2):​c.1655_1656delGTinsAC​(p.Arg552His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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)
• Consequence: PADI2 NM_007365.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.44
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI2	NM_007365.3	MANE Select	c.1655_1656delGTinsAC	p.Arg552His	missense	N/A	NP_031391.2	Q9Y2J8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI2	ENST00000375486.9	TSL:1 MANE Select	c.1655_1656delGTinsAC	p.Arg552His	missense	N/A	ENSP00000364635.4	Q9Y2J8-1
	PADI2	ENST00000908716.1		c.1721_1722delGTinsAC	p.Arg574His	missense	N/A	ENSP00000578775.1
	PADI2	ENST00000945841.1		c.1703_1704delGTinsAC	p.Arg568His	missense	N/A	ENSP00000615900.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-17396691;