Genetic Variant PHF2:p.Arg107Pro (chr9-93645649-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is . The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005392.4(PHF2):c.320G>C(p.Arg107Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,452,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R107H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PHF2
NM_005392.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.38

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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new If you want to explore the variant's impact on the transcript NM_005392.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.320G>C	p.Arg107Pro	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.320G>C	p.Arg107Pro	missense	Exon 4 of 22	ENSP00000352185.4	O75151
PHF2	ENST00000851896.1		c.320G>C	p.Arg107Pro	missense	Exon 4 of 22	ENSP00000521955.1
PHF2	ENST00000937581.1		c.320G>C	p.Arg107Pro	missense	Exon 4 of 22	ENSP00000607640.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33234

American (AMR)

AF:

0.00

AC:

AN:

43884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25604

East Asian (EAS)

AF:

0.00

AC:

AN:

39460

South Asian (SAS)

AF:

0.00

AC:

AN:

85308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106174

Other (OTH)

AF:

0.00

AC:

AN:

59908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

0.029

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.086

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.2

PhyloP100

6.4

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.36

Sift

Uncertain

0.014

Sift4G

Uncertain

0.054

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.84

gMVP

0.88

Mutation Taster

=37/63

disease causing

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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PHF2 p.Arg107Pro

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