Genetic Variant PHF2:p.Pro109Ser (chr9-93645654-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_005392.4(PHF2):c.325C>T(p.Pro109Ser) 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. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P109L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PHF2
NM_005392.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.89

Publications

0 publications found

Variant links:

Genes affected

PHF2 (HGNC:8920): (PHD finger protein 2) This gene encodes a protein which contains a zinc finger-like PHD (plant homeodomain) finger, distinct from other classes of zinc finger motifs, and a hydrophobic and highly conserved domain. The PHD finger shows the typical Cys4-His-Cys3 arrangement. PHD finger genes are thought to belong to a diverse group of transcriptional regulators possibly affecting eukaryotic gene expression by influencing chromatin structure. [provided by RefSeq, Jul 2008]

PHF2 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=0.09124684).

BP6

Variant 9-93645654-C-T is Benign according to our data. Variant chr9-93645654-C-T is described in ClinVar as Benign. ClinVar VariationId is 1686052.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005392.4. 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
	PHF2	NM_005392.4	MANE Select	c.325C>T	p.Pro109Ser	missense	Exon 4 of 22	NP_005383.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF2	ENST00000359246.9	TSL:1 MANE Select	c.325C>T	p.Pro109Ser	missense	Exon 4 of 22	ENSP00000352185.4	O75151
PHF2	ENST00000851896.1		c.325C>T	p.Pro109Ser	missense	Exon 4 of 22	ENSP00000521955.1
PHF2	ENST00000937581.1		c.325C>T	p.Pro109Ser	missense	Exon 4 of 22	ENSP00000607640.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.87e-7

AC:

AN:

1454838

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33334

American (AMR)

AF:

0.00

AC:

AN:

44116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25768

East Asian (EAS)

AF:

0.00

AC:

AN:

39526

South Asian (SAS)

AF:

0.00

AC:

AN:

85582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107858

Other (OTH)

AF:

0.00

AC:

AN:

60012

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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.012

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

M_CAP

Benign

0.027

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.025

PhyloP100

1.9

PrimateAI

Benign

0.42

PROVEAN

Benign

0.31

REVEL

Benign

0.10

Sift

Benign

0.45

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.054

MutPred

0.27

Gain of phosphorylation at P109 (P = 0.0409)

MVP

0.16

MPC

0.54

ClinPred

0.34

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.12

gMVP

0.50

Mutation Taster

=95/5

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

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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