2-44218542-GTTTTA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002706.6(PPM1B):c.1134+14_1134+18del variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00204 in 1,565,766 control chromosomes in the GnomAD database, including 52 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (24 hom.)
• Consequence: PPM1B NM_002706.6 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.68

Genes affected

PPM1B (HGNC:9276): (protein phosphatase, Mg2+/Mn2+ dependent 1B) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase has been shown to dephosphorylate cyclin-dependent kinases (CDKs), and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to cause cell-growth arrest or cell death. Alternative splicing results in multiple transcript variants encoding different isoforms. Additional transcript variants have been described, but currently do not represent full-length sequences. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-44218542-GTTTTA-G is Benign according to our data. Variant chr2-44218542-GTTTTA-G is described in ClinVar as [Benign]. Clinvar id is 788956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1728/152062) while in subpopulation AFR AF= 0.0397 (1645/41474). AF 95% confidence interval is 0.0381. There are 28 homozygotes in gnomad4. There are 837 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1B	NM_002706.6	c.1134+14_1134+18del		splice_donor_region_variant, intron_variant		ENST00000282412.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1B	ENST00000282412.9	c.1134+14_1134+18del		splice_donor_region_variant, intron_variant		1	NM_002706.6

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1723 AN: 151944 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00817

GnomAD3 exomes AF: 0.00297 AC: 670 AN: 225626 Hom.: 12 AF XY: 0.00222 AC XY: 271 AN XY: 122334

Gnomad AFR exome AF: 0.0383

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00164

Gnomad EAS exome AF: 0.000122

Gnomad SAS exome AF: 0.0000410

Gnomad FIN exome AF: 0.0000474

Gnomad NFE exome AF: 0.000103

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00104 AC: 1467 AN: 1413704 Hom.: 24 AF XY: 0.000906 AC XY: 638 AN XY: 704388

Gnomad4 AFR exome AF: 0.0371

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.0000512

Gnomad4 SAS exome AF: 0.0000504

Gnomad4 FIN exome AF: 0.000132

Gnomad4 NFE exome AF: 0.0000810

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.0114 AC: 1728 AN: 152062 Hom.: 28 Cov.: 32 AF XY: 0.0113 AC XY: 837 AN XY: 74350

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00808

Alfa AF: 0.00662 Hom.: 3

Bravo AF: 0.0130

Asia WGS AF: 0.00289 AC: 10 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 25, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201620412; hg19: chr2-44445681;