9-93645701-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005392.4(PHF2):c.372C>T(p.Thr124=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.95

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]

ACMG classification

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/exons	MANE	UniProt
PHF2	NM_005392.4	c.372C>T	p.Thr124=	synonymous_variant	4/22	ENST00000359246.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF2	ENST00000359246.9	c.372C>T	p.Thr124=	synonymous_variant	4/22	1	NM_005392.4	P1
PHF2	ENST00000610682.1	c.239+9236C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21397 AN: 152170 Hom.: 1585 Cov.: 33

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

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.: 34 AF XY: 0.161 AC XY: 116807 AN XY: 726232

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.: 33 AF XY: 0.135 AC XY: 10086 AN XY: 74460

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2019

- -

PHF2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

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

Other links and lift over

dbSNP: rs9695734; hg19: chr9-96407983; COSMIC: COSV63682956;