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GeneBe

9-93645671-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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 (★).

Frequency

Genomes: 𝑓 0.021 ( 44 hom., cov: 34)
Exomes 𝑓: 0.018 ( 301 hom. )

Consequence

PHF2
NM_005392.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.63 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 3197 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHF2NM_005392.4 linkuse as main transcriptc.342G>A p.Thr114= synonymous_variant 4/22 ENST00000359246.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHF2ENST00000359246.9 linkuse as main transcriptc.342G>A p.Thr114= synonymous_variant 4/221 NM_005392.4 P1
PHF2ENST00000610682.1 linkuse as main transcriptc.239+9206G>A intron_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0210
AC:
3197
AN:
152224
Hom.:
44
Cov.:
34
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.:
68
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.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0210
AC:
3199
AN:
152342
Hom.:
44
Cov.:
34
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.:
16
Bravo
AF:
0.0181
Asia WGS
AF:
0.0190
AC:
66
AN:
3478
EpiCase
AF:
0.0179
EpiControl
AF:
0.0177

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PHF2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 28, 2019This 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.

Other links and lift over

dbSNP: rs35505758; hg19: chr9-96407953; API