Genetic Variant NM_006245.4:c.28-35C>T (chr6-42989576-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006245.4(PPP2R5D):c.28-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000751 in 1,544,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

PPP2R5D
NM_006245.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.323

Publications

0 publications found

Variant links:

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]

PPP2R5D Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Hogue-Janssens syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

PPP2R5D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-42989576-C-T is Benign according to our data. Variant chr6-42989576-C-T is described in ClinVar as Benign. ClinVar VariationId is 1296832.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 59 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP2R5D	NM_006245.4	MANE Select	c.28-35C>T	intron	N/A	NP_006236.1	Q14738-1
PPP2R5D	NM_180976.3		c.28-35C>T	intron	N/A	NP_851307.1	Q14738-2
PPP2R5D	NM_180977.3		c.27+4872C>T	intron	N/A	NP_851308.1	Q14738-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP2R5D	ENST00000485511.6	TSL:1 MANE Select	c.28-35C>T	intron	N/A	ENSP00000417963.1	Q14738-1
PPP2R5D	ENST00000394110.7	TSL:1	c.28-35C>T	intron	N/A	ENSP00000377669.3	Q14738-2
PPP2R5D	ENST00000461010.5	TSL:1	c.27+4872C>T	intron	N/A	ENSP00000420674.1	Q14738-3

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000115

AC:

AN:

234238

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00164

Gnomad AMR exome

AF:

0.0000302

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:

0.000345

GnomAD4 exome

AF:

0.0000410

AC:

AN:

1391788

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

694580

show subpopulations

African (AFR)

AF:

0.00148

AC:

AN:

31778

American (AMR)

AF:

0.0000231

AC:

AN:

43332

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

39056

South Asian (SAS)

AF:

0.00

AC:

AN:

83396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52846

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

9.50e-7

AC:

AN:

1052236

Other (OTH)

AF:

0.000121

AC:

AN:

58060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000387

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

41590

American (AMR)

AF:

0.0000653

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.8

(source)

DANN

Benign

0.31

PhyloP100

-0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over