5-134197777-G-GGAA

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4_SupportingPP5_Moderate

The NM_002715.4(PPP2CA):​c.924_925insTTC​(p.Phe308dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PPP2CA
NM_002715.4 inframe_insertion

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 5.44
Variant links:
Genes affected
PPP2CA (HGNC:9299): (protein phosphatase 2 catalytic subunit alpha) This gene encodes the phosphatase 2A catalytic subunit. 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. This gene encodes an alpha isoform of the catalytic subunit. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_002715.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 5-134197777-G-GGAA is Pathogenic according to our data. Variant chr5-134197777-G-GGAA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 620081.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP2CANM_002715.4 linkuse as main transcriptc.924_925insTTC p.Phe308dup inframe_insertion 7/7 ENST00000481195.6
PPP2CANM_001355019.2 linkuse as main transcriptc.729_730insTTC p.Phe243dup inframe_insertion 7/7
PPP2CANR_149151.2 linkuse as main transcriptn.1179_1180insTTC non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP2CAENST00000481195.6 linkuse as main transcriptc.924_925insTTC p.Phe308dup inframe_insertion 7/71 NM_002715.4 P4P67775-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Houge-Janssens syndrome 3 Pathogenic:2
Likely pathogenic, criteria provided, single submittercurationSIB Swiss Institute of BioinformaticsJul 15, 2019This variant is interpreted as a Likely pathogenic for Neurodevelopmental disorder and language delay with or without structural brain abnormalities, autosomal dominant. The following ACMG Tag(s) were applied: PM2, PM6, PS3. -
Pathogenic, no assertion criteria providedliterature onlyOMIMNov 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs864622012; hg19: chr5-133533468; API