Variant 12-56328276-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBA1

The NM_014871.6(PAN2):c.535A>C(p.Ile179Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,607,762 control chromosomes in the GnomAD database, including 768,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.85 ( 58916 hom., cov: 32)

Exomes 𝑓: 0.98 ( 709426 hom. )

Consequence

PAN2
NM_014871.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.59

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PAN2. . Gene score misZ 3.1762 (greater than the threshold 3.09). Trascript score misZ 4.8346 (greater than threshold 3.09). GenCC has associacion of gene with multiple congenital anomalies/dysmorphic syndrome-intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=6.695101E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAN2	NM_014871.6 linkuse as main transcript	c.535A>C	p.Ile179Leu	missense_variant	4/26	ENST00000440411.8	NP_055686.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAN2	ENST00000440411.8 linkuse as main transcript	c.535A>C	p.Ile179Leu	missense_variant	4/26	1	NM_014871.6	ENSP00000388231	P4	Q504Q3-2

Frequencies

GnomAD3 genomes

AF:

0.850

AC:

129276

AN:

152076

Hom.:

58908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.978

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.903

GnomAD3 exomes

AF:

0.959

AC:

236720

AN:

246810

Hom.:

115603

AF XY:

0.970

AC XY:

129309

AN XY:

133348

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.972

Gnomad ASJ exome

AF:

0.981

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.977

GnomAD4 exome

AF:

0.984

AC:

1432197

AN:

1455568

Hom.:

709426

Cov.:

AF XY:

0.986

AC XY:

713556

AN XY:

723592

show subpopulations

Gnomad4 AFR exome

AF:

0.468

Gnomad4 AMR exome

AF:

0.968

Gnomad4 ASJ exome

AF:

0.981

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.964

GnomAD4 genome

AF:

0.850

AC:

129319

AN:

152194

Hom.:

58916

Cov.:

AF XY:

0.855

AC XY:

63655

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.482

Gnomad4 AMR

AF:

0.936

Gnomad4 ASJ

AF:

0.978

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.904

Alfa

AF:

0.969

Hom.:

114370

Bravo

AF:

0.829

TwinsUK

AF:

0.999

AC:

3703

ALSPAC

AF:

0.999

AC:

3851

ESP6500AA

AF:

0.494

AC:

2178

ESP6500EA

AF:

0.996

AC:

8567

ExAC

AF:

0.951

AC:

115375

Asia WGS

AF:

0.971

AC:

3377

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.0020

DANN

Benign

0.69

DEOGEN2

Benign

0.041

T;T;.;.;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.24

.;T;T;T;.;T

MetaRNN

Benign

6.7e-7

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L;L;L;L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.68

N;.;N;N;N;N

REVEL

Benign

0.086

Sift

Benign

0.28

T;.;T;T;T;T

Sift4G

Benign

0.19

T;T;T;T;T;.

Polyphen

0.0010

B;B;B;B;B;.

Vest4

0.076

MutPred

0.48

Gain of catalytic residue at L174 (P = 0);Gain of catalytic residue at L174 (P = 0);Gain of catalytic residue at L174 (P = 0);Gain of catalytic residue at L174 (P = 0);Gain of catalytic residue at L174 (P = 0);.;

MPC

0.51

ClinPred

0.011

GERP RS

-8.8

Varity_R

0.044

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over