dbSNP rs377749543: PCGF2:c.*9A>T (chr17-38735214-T-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_007144.3(PCGF2):c.*9A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,396,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

PCGF2
NM_007144.3 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0330

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-38735214-T-A is Benign according to our data. Variant chr17-38735214-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3048124.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 28 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007144.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PCGF2	NM_007144.3	MANE Select	c.*9A>T	3_prime_UTR	Exon 11 of 11	NP_009075.1	P35227
CISD3	NM_001136498.2	MANE Select	c.*1759T>A	3_prime_UTR	Exon 4 of 4	NP_001129970.1	P0C7P0
PCGF2	NM_001369614.1		c.*9A>T	3_prime_UTR	Exon 10 of 10	NP_001356543.1	P35227

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PCGF2	ENST00000620225.5	TSL:1 MANE Select	c.*9A>T	3_prime_UTR	Exon 11 of 11	ENSP00000482815.1	P35227
CISD3	ENST00000613478.2	TSL:2 MANE Select	c.*1759T>A	3_prime_UTR	Exon 4 of 4	ENSP00000483781.1	P0C7P0
PCGF2	ENST00000611883.4	TSL:1	c.*9A>T	3_prime_UTR	Exon 10 of 10	ENSP00000478970.1	P35227

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

150962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00185

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000638

AC:

AN:

67418

AF XY:

0.000422

show subpopulations

Gnomad AFR exome

AF:

0.000158

Gnomad AMR exome

AF:

0.00426

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00105

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1245446

Hom.:

Cov.:

AF XY:

0.0000433

AC XY:

AN XY:

600888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27408

American (AMR)

AF:

0.00396

AC:

AN:

18444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17330

East Asian (EAS)

AF:

0.00

AC:

AN:

32496

South Asian (SAS)

AF:

0.00

AC:

AN:

54262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4906

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

997390

Other (OTH)

AF:

0.0000394

AC:

AN:

50712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000185

AC:

AN:

151076

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

73782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41076

American (AMR)

AF:

0.00184

AC:

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67708

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000586

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PCGF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.9

(source)

DANN

Benign

0.81

PhyloP100

-0.033

PromoterAI

0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over