12-56328274-TAT-AAG

Variant names:

• chr12-56328274-TAT-AAG
• NM_014871.6:c.535_537delATAinsCTT
• PAN2 p.Ile179Leu

Variant summary

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

The NM_014871.6(PAN2):​c.535_537delATAinsCTT​(p.Ile179Leu) variant causes a missense change involving the alteration of a non-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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAN2 NM_014871.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 0 publications found

Genes affected

PAN2 (HGNC:20074): (poly(A) specific ribonuclease subunit PAN2) This gene encodes a deadenylase that functions as the catalytic subunit of the polyadenylate binding protein dependent poly(A) nuclease complex. The encoded protein is a magnesium dependent 3' to 5' exoribonuclease that is involved in the degradation of cytoplasmic mRNAs. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

PAN2 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome-intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014871.6. 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
	PAN2	NM_014871.6	MANE Select	c.535_537delATAinsCTT	p.Ile179Leu	missense	N/A	NP_055686.4
	PAN2	NM_001127460.4		c.535_537delATAinsCTT	p.Ile179Leu	missense	N/A	NP_001120932.2	Q504Q3-1
	PAN2	NM_001394699.1		c.535_537delATAinsCTT	p.Ile179Leu	missense	N/A	NP_001381628.1	Q504Q3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAN2	ENST00000440411.8	TSL:1 MANE Select	c.535_537delATAinsCTT	p.Ile179Leu	missense	N/A	ENSP00000388231.3	Q504Q3-2
	PAN2	ENST00000425394.7	TSL:1	c.535_537delATAinsCTT	p.Ile179Leu	missense	N/A	ENSP00000401721.2	Q504Q3-1
	PAN2	ENST00000257931.9	TSL:1	c.535_537delATAinsCTT	p.Ile179Leu	missense	N/A	ENSP00000257931.5	Q504Q3-3

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		3.3

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: chr12-56722058;