NM_014225.6:c.75T>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_StrongBP7BS2

The NM_014225.6(PPP2R1A):c.75T>G(p.Val25Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 1,550,678 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 3 hom. )

Consequence

PPP2R1A
NM_014225.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.170

Publications

0 publications found

Variant links:

Genes affected

PPP2R1A (HGNC:9302): (protein phosphatase 2 scaffold subunit Aalpha) This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 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 constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R1A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Houge-Janssens syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P

PPP2R1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP6

Variant 19-52190171-T-G is Benign according to our data. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-52190171-T-G is described in CliVar as Benign/Likely_benign. Clinvar id is 135073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.17 with no splicing effect.

BS2

High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R1A	NM_014225.6 link	c.75T>G	p.Val25Val	synonymous_variant	Exon 1 of 15	ENST00000322088.11	NP_055040.2	P30153A8K7B7
PPP2R1A	NR_033500.2 link	n.120T>G		non_coding_transcript_exon_variant	Exon 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R1A	ENST00000322088.11 link	c.75T>G	p.Val25Val	synonymous_variant	Exon 1 of 15	1	NM_014225.6	ENSP00000324804.6		P30153

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000540

AC:

AN:

153564

AF XY:

0.000505

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000809

Gnomad ASJ exome

AF:

0.00733

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000206

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.000201

AC:

281

AN:

1398532

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

141

AN XY:

689824

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31502

American (AMR)

AF:

0.000168

AC:

AN:

35678

Ashkenazi Jewish (ASJ)

AF:

0.00799

AC:

201

AN:

25152

East Asian (EAS)

AF:

0.00

AC:

AN:

35646

South Asian (SAS)

AF:

0.00

AC:

AN:

79224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000399

AC:

AN:

1078662

Other (OTH)

AF:

0.000535

AC:

AN:

57986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000217

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000658

Hom.:

Bravo

AF:

0.000257

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PPP2R1A: BP4, BP7 -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Houge-Janssens syndrome 2

Benign:1

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

-0.17

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over