chr17-38735233-G-C

Variant names:

• chr17-38735233-G-C
• rs770193210
• NM_007144.3:c.1025C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_007144.3(PCGF2):​c.1025C>G​(p.Pro342Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000077 in 1,428,530 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P342H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: PCGF2 NM_007144.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 5.16
• Publications: 1 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.13649678).
• BP6: Variant 17-38735233-G-C is Benign according to our data. Variant chr17-38735233-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2159950.
• BS2: High AC in GnomAdExome4 at 8 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF2	NM_007144.3	MANE Select	c.1025C>G	p.Pro342Arg	missense	Exon 11 of 11	NP_009075.1	P35227
	CISD3	NM_001136498.2	MANE Select	c.*1778G>C		3_prime_UTR	Exon 4 of 4	NP_001129970.1	P0C7P0
	PCGF2	NM_001369614.1		c.1025C>G	p.Pro342Arg	missense	Exon 10 of 10	NP_001356543.1	P35227

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF2	ENST00000620225.5	TSL:1 MANE Select	c.1025C>G	p.Pro342Arg	missense	Exon 11 of 11	ENSP00000482815.1	P35227
	PCGF2	ENST00000611883.4	TSL:1	c.1025C>G	p.Pro342Arg	missense	Exon 10 of 10	ENSP00000478970.1	P35227
	PCGF2	ENST00000616199.4	TSL:1	c.1025C>G	p.Pro342Arg	missense	Exon 12 of 12	ENSP00000482063.1	P35227

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000492 AC: 4 AN: 81246 AF XY: 0.0000247

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000332

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: 0.00

GnomAD4 exome AF: 0.00000627 AC: 8 AN: 1276250 Hom.: 0 Cov.: 33 AF XY: 0.00000486 AC XY: 3 AN XY: 617606

African (AFR) AF: 0.00 AC: 0 AN: 28384

American (AMR) AF: 0.000232 AC: 5 AN: 21532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18140

East Asian (EAS) AF: 0.00 AC: 0 AN: 33780

South Asian (SAS) AF: 0.00 AC: 0 AN: 60456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5086

European-Non Finnish (NFE) AF: 0.00000198 AC: 2 AN: 1012644

Other (OTH) AF: 0.0000191 AC: 1 AN: 52292

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74460

African (AFR) AF: 0.0000481 AC: 2 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000284 AC: 3

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.081
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.2
PrimateAI	Uncertain	0.63	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0050	B
Vest4		0.15
MutPred		0.26		Gain of MoRF binding (P = 2e-04)
MVP		0.63
ClinPred		0.085	T
GERP RS		4.2
PromoterAI		-0.050	Neutral
Varity_R		0.15
gMVP		0.42
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs770193210; hg19: chr17-36891486;