9-93649079-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005392.4(PHF2):​c.469C>T​(p.Arg157Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,399,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

PHF2
NM_005392.4 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.36813444).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHF2NM_005392.4 linkc.469C>T p.Arg157Trp missense_variant Exon 5 of 22 ENST00000359246.9 NP_005383.3 O75151

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHF2ENST00000359246.9 linkc.469C>T p.Arg157Trp missense_variant Exon 5 of 22 1 NM_005392.4 ENSP00000352185.4 O75151
PHF2ENST00000610682.1 linkc.239+12614C>T intron_variant Intron 3 of 7 5 ENSP00000479936.1 A0A087WW48
PHF2ENST00000375376.8 linkc.187-4188C>T intron_variant Intron 3 of 8 5 E7ET14

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000929
AC:
13
AN:
1399284
Hom.:
0
Cov.:
32
AF XY:
0.00000869
AC XY:
6
AN XY:
690156
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000927
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.469C>T (p.R157W) alteration is located in exon 5 (coding exon 5) of the PHF2 gene. This alteration results from a C to T substitution at nucleotide position 469, causing the arginine (R) at amino acid position 157 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.35
T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.37
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-5.0
D
REVEL
Benign
0.21
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0060
D
Polyphen
1.0
D
Vest4
0.47
MutPred
0.48
Loss of disorder (P = 0.0191);
MVP
0.28
MPC
0.55
ClinPred
0.95
D
GERP RS
2.5
Varity_R
0.48
gMVP
0.92

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.

Other links and lift over

dbSNP: rs1357002895; hg19: chr9-96411361; API