Genetic Variant PCGF2:c.*527A>G (chr17-38734696-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007144.3(PCGF2):c.*527A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,478 control chromosomes in the GnomAD database, including 17,665 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 0.48 ( 17579 hom., cov: 31)

Exomes 𝑓: 0.50 ( 86 hom. )

Consequence

PCGF2
NM_007144.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.827

Variant links:

Genes affected

PCGF2 (HGNC:12929): (polycomb group ring finger 2) The protein encoded by this gene contains a RING finger motif and is similar to the polycomb group (PcG) gene products. PcG gene products form complexes via protein-protein interaction and maintain the transcription repression of genes involved in embryogenesis, cell cycles, and tumorigenesis. This protein was shown to act as a negative regulator of transcription and has tumor suppressor activity. The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. Knockout studies in mice suggested that this protein may negatively regulate the expression of different cytokines, chemokines, and chemokine receptors, and thus plays an important role in lymphocyte differentiation and migration, as well as in immune responses. [provided by RefSeq, Jul 2008]

PCGF2 links:

CISD3 (HGNC:27578): (CDGSH iron sulfur domain 3) CISD3 is a member of the CDGSH domain-containing family, which may play a role in regulating electron transport and oxidative phosphorylation (Wiley et al., 2007 [PubMed 17376863]).[supplied by OMIM, Apr 2008]

CISD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCGF2	NM_007144.3 link	c.*527A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000620225.5	NP_009075.1	P35227A0A024R1V6
CISD3	NM_001136498.2 link	c.*1241T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000613478.2	NP_001129970.1	P0C7P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCGF2	ENST00000620225 link	c.*527A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_007144.3	ENSP00000482815.1		P35227
CISD3	ENST00000613478.2 link	c.*1241T>C		3_prime_UTR_variant	Exon 4 of 4	2	NM_001136498.2	ENSP00000483781.1		P0C7P0

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

72562

AN:

151710

Hom.:

17555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.500

AC:

325

AN:

650

Hom.:

Cov.:

AF XY:

0.505

AC XY:

194

AN XY:

384

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.444

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.478

AC:

72630

AN:

151828

Hom.:

17579

Cov.:

AF XY:

0.480

AC XY:

35600

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.422

Gnomad4 ASJ

AF:

0.395

Gnomad4 EAS

AF:

0.281

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.572

Gnomad4 NFE

AF:

0.483

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.463

Hom.:

25991

Bravo

AF:

0.464

Asia WGS

AF:

0.431

AC:

1498

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.18

DANN

Benign

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over