rs12238738

Variant names:

• chr9-93631525-A-G
• rs12238738
• NM_005392.4:c.184+1470A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005392.4(PHF2):​c.184+1470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,186 control chromosomes in the GnomAD database, including 7,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7447 hom., cov: 33)
• Consequence: PHF2 NM_005392.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 8 publications found

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF2	NM_005392.4	c.184+1470A>G		intron_variant	Intron 2 of 21	ENST00000359246.9	NP_005383.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF2	ENST00000359246.9	c.184+1470A>G		intron_variant	Intron 2 of 21	1	NM_005392.4	ENSP00000352185.4
PHF2	ENST00000610682.1	c.184+1470A>G		intron_variant	Intron 2 of 7	5		ENSP00000479936.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42137 AN: 152068 Hom.: 7449 Cov.: 33

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 42132 AN: 152186 Hom.: 7447 Cov.: 33 AF XY: 0.274 AC XY: 20392 AN XY: 74416

African (AFR) AF: 0.0697 AC: 2897 AN: 41550

American (AMR) AF: 0.278 AC: 4248 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1460 AN: 5166

South Asian (SAS) AF: 0.153 AC: 736 AN: 4824

European-Finnish (FIN) AF: 0.379 AC: 4018 AN: 10604

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26624 AN: 67966

Other (OTH) AF: 0.292 AC: 618 AN: 2116

Alfa AF: 0.335 Hom.: 1706

Bravo AF: 0.258

Asia WGS AF: 0.189 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.62
PhyloP100		0.19
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs12238738; hg19: chr9-96393807; COSMIC: COSV63680745;