Genetic Variant POU2AF1:p.Pro164Gln (chr11-111354541-G-T) – 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_006235.3(POU2AF1):c.491C>A(p.Pro164Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P164L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

POU2AF1
NM_006235.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.313

Publications

0 publications found

Variant links:

Genes affected

POU2AF1 (HGNC:9211): (POU class 2 homeobox associating factor 1) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of RNA polymerase II transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

POU2AF1 Gene-Disease associations (from GenCC):

agammaglobulinemia
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

POU2AF1 links:

Genome browser will be placed here

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=0.0559749).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006235.3. 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
	POU2AF1	NM_006235.3	MANE Select	c.491C>A	p.Pro164Gln	missense	Exon 5 of 5	NP_006226.2	Q16633

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF1	ENST00000393067.8	TSL:1 MANE Select	c.491C>A	p.Pro164Gln	missense	Exon 5 of 5	ENSP00000376786.3	Q16633
	POU2AF1	ENST00000525584.1	TSL:3	n.610C>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1396808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690170

show subpopulations

African (AFR)

AF:

0.0000329

AC:

AN:

30378

American (AMR)

AF:

0.00

AC:

AN:

29882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22140

East Asian (EAS)

AF:

0.00

AC:

AN:

38634

South Asian (SAS)

AF:

0.00

AC:

AN:

75994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5318

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085330

Other (OTH)

AF:

0.00

AC:

AN:

57410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.1

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.094

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.72

M_CAP

Benign

0.0029

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.63

PhyloP100

0.31

PrimateAI

Benign

0.39

PROVEAN

Benign

0.96

REVEL

Benign

0.040

Sift

Benign

1.0

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.094

MutPred

0.34

Loss of glycosylation at P164 (P = 0.0551)

MVP

0.043

MPC

0.25

ClinPred

0.070

GERP RS

-0.63

Varity_R

0.042

gMVP

0.31

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over