dbSNP rs1918496: PAN2:p.Ile179Val (chr12-56328276-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_014871.6(PAN2):c.535A>G(p.Ile179Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAN2
NM_014871.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.59

Publications

31 publications found

Variant links:

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

PAN2 links:

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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=0.067320645).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAN2	NM_014871.6	MANE Select	c.535A>G	p.Ile179Val	missense	Exon 4 of 26	NP_055686.4
PAN2	NM_001127460.4		c.535A>G	p.Ile179Val	missense	Exon 4 of 26	NP_001120932.2	Q504Q3-1
PAN2	NM_001394699.1		c.535A>G	p.Ile179Val	missense	Exon 4 of 26	NP_001381628.1	Q504Q3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAN2	ENST00000440411.8	TSL:1 MANE Select	c.535A>G	p.Ile179Val	missense	Exon 4 of 26	ENSP00000388231.3	Q504Q3-2
PAN2	ENST00000425394.7	TSL:1	c.535A>G	p.Ile179Val	missense	Exon 4 of 26	ENSP00000401721.2	Q504Q3-1
PAN2	ENST00000257931.9	TSL:1	c.535A>G	p.Ile179Val	missense	Exon 4 of 26	ENSP00000257931.5	Q504Q3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723600

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

43994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25662

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

85382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108574

Other (OTH)

AF:

0.00

AC:

AN:

60098

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.047

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.037

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.27

M_CAP

Benign

0.016

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

-2.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.48

REVEL

Benign

0.045

Sift

Benign

0.14

Sift4G

Benign

0.23

Polyphen

0.0010

Vest4

0.033

MutPred

0.48

Gain of catalytic residue at L174 (P = 1e-04)

MVP

0.51

MPC

0.43

ClinPred

0.092

GERP RS

-8.8

Varity_R

0.017

gMVP

0.068

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over