9-93653195-G-C

Variant names:

• chr9-93653195-G-C
• NM_005392.4:c.619G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005392.4(PHF2):​c.619G>C​(p.Glu207Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PHF2 NM_005392.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.85

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF2	NM_005392.4	c.619G>C	p.Glu207Gln	missense_variant	Exon 6 of 22	ENST00000359246.9	NP_005383.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF2	ENST00000359246.9	c.619G>C	p.Glu207Gln	missense_variant	Exon 6 of 22	1	NM_005392.4	ENSP00000352185.4
PHF2	ENST00000610682.1	c.239+16730G>C		intron_variant	Intron 3 of 7	5		ENSP00000479936.1
PHF2	ENST00000375376.8	c.187-72G>C		intron_variant	Intron 3 of 8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.619G>C (p.E207Q) alteration is located in exon 6 (coding exon 6) of the PHF2 gene. This alteration results from a G to C substitution at nucleotide position 619, causing the glutamic acid (E) at amino acid position 207 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.015	D
Polyphen		0.83	P
Vest4		0.55
MutPred		0.33		Loss of phosphorylation at S204 (P = 0.0877);
MVP		0.46
MPC		0.53
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.73
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-96415477;