9-93645671-G-A

Variant names:

• chr9-93645671-G-A
• rs35505758
• NM_005392.4:c.342G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_005392.4(PHF2):​c.342G>A​(p.Thr114Thr) 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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.63

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 -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 the male GnomAd4 subpopulation. Median coverage is 34. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 3199 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF2	NM_005392.4	c.342G>A	p.Thr114Thr	synonymous_variant	Exon 4 of 22	ENST00000359246.9	NP_005383.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF2	ENST00000359246.9	c.342G>A	p.Thr114Thr	synonymous_variant	Exon 4 of 22	1	NM_005392.4	ENSP00000352185.4
PHF2	ENST00000610682.1	c.239+9206G>A		intron_variant	Intron 3 of 7	5		ENSP00000479936.1
PHF2	ENST00000375376.8	c.187-7596G>A		intron_variant	Intron 3 of 8	5

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3197 AN: 152224 Hom.: 44 Cov.: 34

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

GnomAD2 exomes AF: 0.0188 AC: 4706 AN: 249840 AF XY: 0.0192

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 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

Gnomad4 AFR exome AF: 0.0236 AC: 789 AN: 33408

Gnomad4 AMR exome AF: 0.0101 AC: 451 AN: 44528

Gnomad4 ASJ exome AF: 0.0215 AC: 561 AN: 26048

Gnomad4 EAS exome AF: 0.00976 AC: 387 AN: 39636

Gnomad4 SAS exome AF: 0.0187 AC: 1612 AN: 86020

Gnomad4 FIN exome AF: 0.0432 AC: 2298 AN: 53204

Gnomad4 NFE exome AF: 0.0170 AC: 18916 AN: 1110484

Gnomad4 Remaining exome AF: 0.0182 AC: 1095 AN: 60216

GnomAD4 genome AF: 0.0210 AC: 3199 AN: 152342 Hom.: 44 Cov.: 34 AF XY: 0.0224 AC XY: 1669 AN XY: 74484

Gnomad4 AFR AF: 0.0207 AC: 0.02069 AN: 0.02069

Gnomad4 AMR AF: 0.0168 AC: 0.0167842 AN: 0.0167842

Gnomad4 ASJ AF: 0.0196 AC: 0.0195965 AN: 0.0195965

Gnomad4 EAS AF: 0.00985 AC: 0.00984556 AN: 0.00984556

Gnomad4 SAS AF: 0.0188 AC: 0.0188328 AN: 0.0188328

Gnomad4 FIN AF: 0.0509 AC: 0.0509416 AN: 0.0509416

Gnomad4 NFE AF: 0.0176 AC: 0.0175627 AN: 0.0175627

Gnomad4 OTH AF: 0.0218 AC: 0.0217597 AN: 0.0217597

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: no assertion criteria provided

Submissions by phenotype

PHF2-related disorder Benign:1

Jun 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
Mutation Taster		=98/2	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

Publications

LitVar

Other links and lift over

dbSNP: rs35505758; hg19: chr9-96407953;