9-93645701-C-T

Variant names:

• chr9-93645701-C-T
• rs9695734
• NM_005392.4:c.372C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.95
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

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.372C>T	p.Thr124Thr	synonymous	Exon 4 of 22	NP_005383.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF2	ENST00000359246.9	TSL:1 MANE Select	c.372C>T	p.Thr124Thr	synonymous	Exon 4 of 22	ENSP00000352185.4	O75151
	PHF2	ENST00000851896.1		c.372C>T	p.Thr124Thr	synonymous	Exon 4 of 22	ENSP00000521955.1
	PHF2	ENST00000937581.1		c.372C>T	p.Thr124Thr	synonymous	Exon 4 of 22	ENSP00000607640.1

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

GnomAD2 exomes AF: 0.131 AC: 32832 AN: 250572 AF XY: 0.133

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 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

African (AFR) AF: 0.122 AC: 4083 AN: 33434

American (AMR) AF: 0.0812 AC: 3623 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4783 AN: 26090

East Asian (EAS) AF: 0.0621 AC: 2463 AN: 39682

South Asian (SAS) AF: 0.113 AC: 9705 AN: 86120

European-Finnish (FIN) AF: 0.121 AC: 6466 AN: 53294

Middle Eastern (MID) AF: 0.160 AC: 819 AN: 5126

European-Non Finnish (NFE) AF: 0.176 AC: 195839 AN: 1111328

Other (OTH) AF: 0.163 AC: 9819 AN: 60274

GnomAD4 genome AF: 0.141 AC: 21408 AN: 152288 Hom.: 1585 Cov.: 33 AF XY: 0.135 AC XY: 10086 AN XY: 74460

African (AFR) AF: 0.127 AC: 5293 AN: 41536

American (AMR) AF: 0.111 AC: 1701 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3470

East Asian (EAS) AF: 0.0469 AC: 243 AN: 5182

South Asian (SAS) AF: 0.111 AC: 536 AN: 4828

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10624

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11384 AN: 68022

Other (OTH) AF: 0.136 AC: 287 AN: 2108

Alfa AF: 0.155 Hom.: 5115

Bravo AF: 0.140

Asia WGS AF: 0.0780 AC: 272 AN: 3478

EpiCase AF: 0.177

EpiControl AF: 0.176

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	PHF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.092
DANN	Benign	0.83
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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