6-42984646-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006245.4(PPP2R5D):c.-32G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00055 in 1,587,956 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (4 hom.)
• Consequence: PPP2R5D NM_006245.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

Genes affected

PPP2R5D (HGNC:9312): (protein phosphatase 2 regulatory subunit B'delta) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a delta isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 6-42984646-G-T is Benign according to our data. Variant chr6-42984646-G-T is described in ClinVar as [Benign]. Clinvar id is 1271131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000611 (93/152296) while in subpopulation AMR AF= 0.00085 (13/15302). AF 95% confidence interval is 0.000502. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 93 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R5D	NM_006245.4	c.-32G>T		5_prime_UTR_variant	1/16	ENST00000485511.6
PPP2R5D	NM_001270476.2	c.-502G>T		5_prime_UTR_variant	1/16
PPP2R5D	NM_180976.3	c.-32G>T		5_prime_UTR_variant	1/16
PPP2R5D	NM_180977.3	c.-32G>T		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5D	ENST00000485511.6	c.-32G>T		5_prime_UTR_variant	1/16	1	NM_006245.4	P1

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000961 AC: 197 AN: 204980 Hom.: 2 AF XY: 0.000984 AC XY: 110 AN XY: 111810

Gnomad AFR exome AF: 0.0000878

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.00773

Gnomad EAS exome AF: 0.0000659

Gnomad SAS exome AF: 0.00146

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000488

Gnomad OTH exome AF: 0.000777

GnomAD4 exome AF: 0.000544 AC: 781 AN: 1435660 Hom.: 4 Cov.: 31 AF XY: 0.000576 AC XY: 410 AN XY: 712274

Gnomad4 AFR exome AF: 0.0000309

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00752

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.00120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000336

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.000611 AC: 93 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74470

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00808

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00150 Hom.: 2

Bravo AF: 0.000752

Asia WGS AF: 0.00318 AC: 11 AN: 3476

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

GeneDx

Jun 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	19
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs189593329; hg19: chr6-42952384;