Genetic Variant PYGO2:p.Met141Ile (chr1-154959577-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138300.4(PYGO2):c.423G>A(p.Met141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,456,446 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 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: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 6 hom. )

Consequence

PYGO2
NM_138300.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Publications

8 publications found

Variant links:

Genes affected

PYGO2 (HGNC:30257): (pygopus family PHD finger 2) Predicted to enable several functions, including chromatin binding activity; histone acetyltransferase regulator activity; and histone binding activity. Predicted to be involved in kidney development and spermatid nucleus differentiation. Predicted to act upstream of or within several processes, including animal organ development; positive regulation of chromatin binding activity; and regulation of histone H3-K4 methylation. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

PYGO2 links:

ENSG00000310191 (HGNC:):

ENSG00000310191 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007651925).

BS2

High AC in GnomAd4 at 412 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGO2	NM_138300.4 link	c.423G>A	p.Met141Ile	missense_variant	Exon 3 of 3	ENST00000368457.3	NP_612157.1	Q9BRQ0Q5T170

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGO2	ENST00000368457.3 link	c.423G>A	p.Met141Ile	missense_variant	Exon 3 of 3	1	NM_138300.4	ENSP00000357442.2		Q9BRQ0

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

414

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00640

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00459

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000839

Gnomad OTH

AF:

0.00576

GnomAD2 exomes

AF:

0.00142

AC:

209

AN:

147278

AF XY:

0.00108

show subpopulations

Gnomad AFR exome

AF:

0.00624

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.000775

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000925

Gnomad OTH exome

AF:

0.00434

GnomAD4 exome

AF:

0.000850

AC:

1109

AN:

1304560

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

515

AN XY:

636288

show subpopulations

African (AFR)

AF:

0.00646

AC:

181

AN:

28016

American (AMR)

AF:

0.00393

AC:

AN:

23134

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

18528

East Asian (EAS)

AF:

0.00

AC:

AN:

34708

South Asian (SAS)

AF:

0.000147

AC:

AN:

61382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48040

Middle Eastern (MID)

AF:

0.00665

AC:

AN:

5114

European-Non Finnish (NFE)

AF:

0.000648

AC:

669

AN:

1032582

Other (OTH)

AF:

0.00194

AC:

103

AN:

53056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

108

162

216

270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00271

AC:

412

AN:

151886

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.00635

AC:

263

AN:

41398

American (AMR)

AF:

0.00459

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.000208

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000839

AC:

AN:

67908

Other (OTH)

AF:

0.00570

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00367

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00148

AC:

172

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

PhyloP100

1.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.029

D;D

Sift4G

Benign

0.40

T;T

Polyphen

0.0050

B;.

Vest4

0.34

MutPred

0.17

Loss of glycosylation at P140 (P = 0.0873);.;

MVP

0.64

MPC

0.30

ClinPred

0.012

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.30

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over