9-93636532-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005392.4(PHF2):c.299+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000988 in 1,564,226 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (4 hom.)
• Consequence: PHF2 NM_005392.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001214
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.417

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-93636532-T-A is Benign according to our data. Variant chr9-93636532-T-A is described in ClinVar as [Benign]. Clinvar id is 731722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 596 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF2	NM_005392.4	c.299+7T>A		splice_region_variant, intron_variant		ENST00000359246.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF2	ENST00000359246.9	c.299+7T>A		splice_region_variant, intron_variant		1	NM_005392.4	P1
PHF2	ENST00000610682.1	c.239+67T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 596 AN: 152196 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00115 AC: 211 AN: 183602 Hom.: 1 AF XY: 0.000881 AC XY: 86 AN XY: 97598

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.000999

Gnomad ASJ exome AF: 0.000568

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000411

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000364

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.000672 AC: 949 AN: 1411912 Hom.: 4 Cov.: 28 AF XY: 0.000591 AC XY: 413 AN XY: 699252

Gnomad4 AFR exome AF: 0.0140

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000619

Gnomad4 FIN exome AF: 0.0000202

Gnomad4 NFE exome AF: 0.000284

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.00391 AC: 596 AN: 152314 Hom.: 1 Cov.: 32 AF XY: 0.00388 AC XY: 289 AN XY: 74470

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.00441

Asia WGS AF: 0.000866 AC: 3 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

Invitae

Sep 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	4.7
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0040
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: rs77405940; hg19: chr9-96398814;