9-93645638-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_005392.4(PHF2):c.309C>T(p.Asp103=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,597,282 control chromosomes in the GnomAD database, including 5,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (433 hom., cov: 34)
  • Exomes 𝑓: 0.083 (5357 hom.)
• Consequence: PHF2 NM_005392.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.76

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 9-93645638-C-T is Benign according to our data. Variant chr9-93645638-C-T is described in ClinVar as [Benign]. Clinvar id is 1278335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF2	NM_005392.4	c.309C>T	p.Asp103=	synonymous_variant	4/22	ENST00000359246.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF2	ENST00000359246.9	c.309C>T	p.Asp103=	synonymous_variant	4/22	1	NM_005392.4	P1
PHF2	ENST00000610682.1	c.239+9173C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10513 AN: 152200 Hom.: 431 Cov.: 34

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.0630

GnomAD3 exomes AF: 0.0703 AC: 16849 AN: 239700 Hom.: 730 AF XY: 0.0700 AC XY: 9048 AN XY: 129258

Gnomad AFR exome AF: 0.0419

Gnomad AMR exome AF: 0.0320

Gnomad ASJ exome AF: 0.0395

Gnomad EAS exome AF: 0.0653

Gnomad SAS exome AF: 0.0406

Gnomad FIN exome AF: 0.0989

Gnomad NFE exome AF: 0.0919

Gnomad OTH exome AF: 0.0707

GnomAD4 exome AF: 0.0832 AC: 120197 AN: 1444964 Hom.: 5357 Cov.: 32 AF XY: 0.0822 AC XY: 58941 AN XY: 717226

Gnomad4 AFR exome AF: 0.0434

Gnomad4 AMR exome AF: 0.0323

Gnomad4 ASJ exome AF: 0.0405

Gnomad4 EAS exome AF: 0.0595

Gnomad4 SAS exome AF: 0.0375

Gnomad4 FIN exome AF: 0.0988

Gnomad4 NFE exome AF: 0.0917

Gnomad4 OTH exome AF: 0.0719

GnomAD4 genome AF: 0.0691 AC: 10521 AN: 152318 Hom.: 433 Cov.: 34 AF XY: 0.0687 AC XY: 5116 AN XY: 74476

Gnomad4 AFR AF: 0.0436

Gnomad4 AMR AF: 0.0474

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0881

Gnomad4 OTH AF: 0.0638

Alfa AF: 0.0753 Hom.: 308

Bravo AF: 0.0659

Asia WGS AF: 0.0660 AC: 227 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	1.8
Dann	Benign	0.66
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: rs7038310; hg19: chr9-96407920; COSMIC: COSV63678235;