chr2-28751600-T-C

Variant names:

• chr2-28751600-T-C
• rs7598876
• ENST00000653462.1:n.123A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000653462.1(PPP1CB-DT):​n.123A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 161,858 control chromosomes in the GnomAD database, including 36,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34223 hom., cov: 36)
  • Exomes 𝑓: 0.64 (2058 hom.)
• Consequence: PPP1CB-DT ENST00000653462.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.14
• Publications: 6 publications found

Genes affected

PPP1CB-DT (HGNC:55829): (PPP1CB divergent transcript)

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]

PPP1CB Gene-Disease associations (from GenCC):

• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome-like disorder with loose anagen hair 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-28751600-T-C is Benign according to our data. Variant chr2-28751600-T-C is described in ClinVar as [Benign]. Clinvar id is 1261656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.-525T>C		upstream_gene_variant		ENST00000395366.3	NP_002700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3	c.-525T>C		upstream_gene_variant		1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101622 AN: 152120 Hom.: 34203 Cov.: 36

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.697

GnomAD4 exome AF: 0.643 AC: 6188 AN: 9620 Hom.: 2058 Cov.: 0 AF XY: 0.640 AC XY: 3328 AN XY: 5204

African (AFR) AF: 0.620 AC: 31 AN: 50

American (AMR) AF: 0.650 AC: 26 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 94 AN: 182

East Asian (EAS) AF: 0.618 AC: 21 AN: 34

South Asian (SAS) AF: 0.669 AC: 1293 AN: 1932

European-Finnish (FIN) AF: 0.639 AC: 327 AN: 512

Middle Eastern (MID) AF: 0.567 AC: 17 AN: 30

European-Non Finnish (NFE) AF: 0.638 AC: 4007 AN: 6278

Other (OTH) AF: 0.662 AC: 372 AN: 562

GnomAD4 genome AF: 0.668 AC: 101686 AN: 152238 Hom.: 34223 Cov.: 36 AF XY: 0.671 AC XY: 49954 AN XY: 74424

African (AFR) AF: 0.602 AC: 25011 AN: 41548

American (AMR) AF: 0.685 AC: 10472 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2268 AN: 3472

East Asian (EAS) AF: 0.722 AC: 3732 AN: 5166

South Asian (SAS) AF: 0.736 AC: 3557 AN: 4832

European-Finnish (FIN) AF: 0.705 AC: 7475 AN: 10602

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47033 AN: 68012

Other (OTH) AF: 0.700 AC: 1478 AN: 2110

Alfa AF: 0.674 Hom.: 4317

Bravo AF: 0.663

Asia WGS AF: 0.745 AC: 2591 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 01, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.43
PhyloP100		-2.1
PromoterAI		0.046	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7598876; hg19: chr2-28974466;