9-93576755-G-GGCGGC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005392.4(PHF2):c.-8_-4dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000094 in 1,170,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000088 (0 hom.)
• Consequence: PHF2 NM_005392.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.696

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 9-93576755-G-GGCGGC is Benign according to our data. Variant chr9-93576755-G-GGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 3044205.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF2	NM_005392.4	c.-8_-4dup		5_prime_UTR_variant	1/22	ENST00000359246.9
PHF2	XM_005252051.3	c.-8_-4dup		5_prime_UTR_variant	1/22
PHF2	XM_006717143.3	c.-8_-4dup		5_prime_UTR_variant	1/22
PHF2	XM_047423475.1	c.-8_-4dup		5_prime_UTR_variant	1/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF2	ENST00000359246.9	c.-8_-4dup		5_prime_UTR_variant	1/22	1	NM_005392.4	P1
PHF2	ENST00000610682.1	c.-8_-4dup		5_prime_UTR_variant	1/8	5

Frequencies

GnomAD3 genomes AF: 0.0000138 AC: 2 AN: 144498 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000307

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000225 AC: 2 AN: 88968 Hom.: 0 AF XY: 0.0000196 AC XY: 1 AN XY: 50928

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000652

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000280

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000877 AC: 9 AN: 1025882 Hom.: 0 Cov.: 23 AF XY: 0.00000596 AC XY: 3 AN XY: 503766

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000541

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000939

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000138 AC: 2 AN: 144498 Hom.: 0 Cov.: 30 AF XY: 0.0000143 AC XY: 1 AN XY: 70174

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000307

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000142 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PHF2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as likely 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1007572113; hg19: chr9-96339037;