rs375528061

Variant names:

• chr9-93649114-G-C
• NM_005392.4:c.504G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-93649114-G-C
• chr9-93649114-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005392.4(PHF2):​c.504G>C​(p.Lys168Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PHF2 NM_005392.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18521306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF2	NM_005392.4	c.504G>C	p.Lys168Asn	missense_variant	Exon 5 of 22	ENST00000359246.9	NP_005383.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF2	ENST00000359246.9	c.504G>C	p.Lys168Asn	missense_variant	Exon 5 of 22	1	NM_005392.4	ENSP00000352185.4
PHF2	ENST00000610682.1	c.239+12649G>C		intron_variant	Intron 3 of 7	5		ENSP00000479936.1
PHF2	ENST00000375376.8	c.187-4153G>C		intron_variant	Intron 3 of 8	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399436 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.13
Sift	Benign	0.13	T
Sift4G	Benign	0.080	T
Polyphen		0.90	P
Vest4		0.24
MutPred		0.40		Gain of ubiquitination at K166 (P = 0.0291);
MVP		0.38
MPC		0.63
ClinPred		0.81	D
GERP RS		0.29
Varity_R		0.40
gMVP		0.84

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: chr9-96411396;