chr2-28783902-T-G

Variant names:

• chr2-28783902-T-G
• rs779498657
• NM_002709.3:c.521-5T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002709.3(PPP1CB):​c.521-5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 1,455,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: PPP1CB NM_002709.3 splice_region, intron
• Scores: Splicing: ADA: 0.004659
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0830
• Publications: 0 publications found

Genes affected

PPP1CB (HGNC:9282): (protein phosphatase 1 catalytic subunit beta) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

SPDYA (HGNC:30613): (speedy/RINGO cell cycle regulator family member A) Enables protein kinase activator activity and protein kinase binding activity. Involved in several processes, including G1/S transition of mitotic cell cycle; positive regulation of cell population proliferation; and positive regulation of protein kinase activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 2-28783902-T-G is Benign according to our data. Variant chr2-28783902-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1633115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 34 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002709.3. 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
	PPP1CB	NM_002709.3	MANE Select	c.521-5T>G		splice_region intron	N/A	NP_002700.1	P62140
	PPP1CB	NM_206876.2		c.521-5T>G		splice_region intron	N/A	NP_996759.1	P62140

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CB	ENST00000395366.3	TSL:1 MANE Select	c.521-5T>G		splice_region intron	N/A	ENSP00000378769.2	P62140
	PPP1CB	ENST00000296122.10	TSL:1	c.521-5T>G		splice_region intron	N/A	ENSP00000296122.6	P62140
	PPP1CB	ENST00000868413.1		c.543T>G	p.Phe181Leu	missense	Exon 5 of 8	ENSP00000538472.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 251066 AF XY: 0.0000663

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: 0.0000234 AC: 34 AN: 1455088 Hom.: 0 Cov.: 28 AF XY: 0.0000331 AC XY: 24 AN XY: 724416

African (AFR) AF: 0.0000300 AC: 1 AN: 33314

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39614

South Asian (SAS) AF: 0.000360 AC: 31 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106118

Other (OTH) AF: 0.0000166 AC: 1 AN: 60182

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.083
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0047
dbscSNV1_RF	Benign	0.19
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: rs779498657; hg19: chr2-29006768;