Variant 9-93645701-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005392.4(PHF2):c.372C>T(p.Thr124Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,612,274 control chromosomes in the GnomAD database, including 21,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1585 hom., cov: 33)

Exomes 𝑓: 0.16 ( 20299 hom. )

Consequence

PHF2
NM_005392.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 9-93645701-C-T is Benign according to our data. Variant chr9-93645701-C-T is described in ClinVar as [Benign]. Clinvar id is 1262733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.95 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF2	NM_005392.4 link	c.372C>T	p.Thr124Thr	synonymous_variant	Exon 4 of 22	ENST00000359246.9	NP_005383.3	O75151

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PHF2	ENST00000359246.9 link	c.372C>T	p.Thr124Thr	synonymous_variant	Exon 4 of 22	1	NM_005392.4	ENSP00000352185.4	O75151
PHF2	ENST00000610682.1 link	c.239+9236C>T		intron_variant	Intron 3 of 7	5		ENSP00000479936.1	A0A087WW48
PHF2	ENST00000375376.8 link	c.187-7566C>T		intron_variant	Intron 3 of 8	5			E7ET14

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21397

AN:

152170

Hom.:

1585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.0472

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.131

AC:

32832

AN:

250572

Hom.:

2448

AF XY:

0.133

AC XY:

18067

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.0772

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.0369

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.163

AC:

237600

AN:

1459986

Hom.:

20299

Cov.:

AF XY:

0.161

AC XY:

116807

AN XY:

726232

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.0812

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.0621

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.141

AC:

21408

AN:

152288

Hom.:

1585

Cov.:

AF XY:

0.135

AC XY:

10086

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.0469

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.157

Hom.:

3475

Bravo

AF:

0.140

Asia WGS

AF:

0.0780

AC:

272

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.176

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PHF2-related disorder

Benign:1

Nov 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.092

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over