X-42777891-G-T

Variant names:

• chrX-42777891-G-T
• rs192382007
• NM_025210.2:c.189C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_025210.2(PPP1R2C):​c.189C>A​(p.Tyr63*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000584 in 513,497 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y63Y) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000050 (0 hom. 0 hem.)
• Consequence: PPP1R2C NM_025210.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 0 publications found

Genes affected

PPP1R2C (HGNC:16324): (PPP1R2C family member C) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in regulation of phosphoprotein phosphatase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025210.2. 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
	PPP1R2C	NM_025210.2	MANE Select	c.189C>A	p.Tyr63*	stop_gained	Exon 1 of 1	NP_079486.1	O14990

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R2C	ENST00000378131.4	TSL:6 MANE Select	c.189C>A	p.Tyr63*	stop_gained	Exon 1 of 1	ENSP00000490336.1	O14990

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111859 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000100 AC: 1 AN: 99790 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000498 AC: 2 AN: 401638 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 149062

African (AFR) AF: 0.00 AC: 0 AN: 12502

American (AMR) AF: 0.00 AC: 0 AN: 27092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14668

East Asian (EAS) AF: 0.00 AC: 0 AN: 24112

South Asian (SAS) AF: 0.0000264 AC: 1 AN: 37887

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25645

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2983

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 233608

Other (OTH) AF: 0.0000432 AC: 1 AN: 23141

GnomAD4 genome AF: 0.00000894 AC: 1 AN: 111859 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34027

African (AFR) AF: 0.0000325 AC: 1 AN: 30762

American (AMR) AF: 0.00 AC: 0 AN: 10645

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3541

South Asian (SAS) AF: 0.00 AC: 0 AN: 2655

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6033

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53148

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	21
DANN	Benign	0.72
FATHMM_MKL	Benign	0.36	N
PhyloP100		-0.065
GERP RS		-2.9
PromoterAI		-0.070	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs192382007; hg19: chrX-42637142;