Variant 9-93645671-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_005392.4(PHF2):c.342G>A(p.Thr114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,611,392 control chromosomes in the GnomAD database, including 345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.021 ( 44 hom., cov: 34)

Exomes 𝑓: 0.018 ( 301 hom. )

Consequence

PHF2
NM_005392.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.63

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 9-93645671-G-A is Benign according to our data. Variant chr9-93645671-G-A is described in ClinVar as [Benign]. Clinvar id is 3038246.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-4.63 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.021 (3199/152342) while in subpopulation AFR AF= 0.0207 (860/41566). AF 95% confidence interval is 0.0195. There are 44 homozygotes in gnomad4. There are 1669 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3199 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF2	NM_005392.4 linkuse as main transcript	c.342G>A	p.Thr114=	synonymous_variant	4/22	ENST00000359246.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF2	ENST00000359246.9 linkuse as main transcript	c.342G>A	p.Thr114=	synonymous_variant	4/22	1	NM_005392.4	P1
PHF2	ENST00000610682.1 linkuse as main transcript	c.239+9206G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3197

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0207

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.0186

Gnomad FIN

AF:

0.0509

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0188

AC:

4706

AN:

249840

Hom.:

AF XY:

0.0192

AC XY:

2596

AN XY:

135042

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.0100

Gnomad ASJ exome

AF:

0.0227

Gnomad EAS exome

AF:

0.00512

Gnomad SAS exome

AF:

0.0178

Gnomad FIN exome

AF:

0.0473

Gnomad NFE exome

AF:

0.0176

Gnomad OTH exome

AF:

0.0211

GnomAD4 exome

AF:

0.0180

AC:

26284

AN:

1459050

Hom.:

301

Cov.:

AF XY:

0.0182

AC XY:

13188

AN XY:

725638

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.00976

Gnomad4 SAS exome

AF:

0.0187

Gnomad4 FIN exome

AF:

0.0432

Gnomad4 NFE exome

AF:

0.0170

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0210

AC:

3199

AN:

152342

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

1669

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0207

Gnomad4 AMR

AF:

0.0168

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00985

Gnomad4 SAS

AF:

0.0188

Gnomad4 FIN

AF:

0.0509

Gnomad4 NFE

AF:

0.0176

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.0181

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0179

EpiControl

AF:

0.0177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PHF2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 28, 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

-0.78

CADD

Benign

0.0090

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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