17-38734696-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

Genes affected

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]

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]

ACMG classification

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/exons	MANE	UniProt
CISD3	NM_001136498.2	c.*1241T>C		3_prime_UTR_variant	4/4	ENST00000613478.2
PCGF2	NM_007144.3	c.*527A>G		3_prime_UTR_variant	11/11	ENST00000620225.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CISD3	ENST00000613478.2	c.*1241T>C		3_prime_UTR_variant	4/4	2	NM_001136498.2	P1
PCGF2	ENST00000620225.5	c.*527A>G		3_prime_UTR_variant	11/11	1	NM_007144.3	P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72562 AN: 151710 Hom.: 17555 Cov.: 31

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.: 86 Cov.: 0 AF XY: 0.505 AC XY: 194 AN XY: 384

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.: 31 AF XY: 0.480 AC XY: 35600 AN XY: 74194

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

Other links and lift over

dbSNP: rs708692; hg19: chr17-36890949;