10-87960952-C-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000314.8(PTEN):c.860C>G(p.Ser287Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S287S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000314.8 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.860C>G | p.Ser287Ter | stop_gained | 8/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.1379C>G | p.Ser460Ter | stop_gained | 9/10 | ||
PTEN | NM_001304718.2 | c.269C>G | p.Ser90Ter | stop_gained | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.860C>G | p.Ser287Ter | stop_gained | 8/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 36
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Malignant tumor of prostate;C1848599:VACTERL with hydrocephalus;C1854416:Macrocephaly-autism syndrome;C1959582:PTEN hamartoma tumor syndrome;C2751642:Glioma susceptibility 2;C3551915:Familial meningioma;CN072330:Cowden syndrome 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | The p.S287* pathogenic mutation (also known as c.860C>G), located in coding exon 8 of the PTEN gene, results from a C to G substitution at nucleotide position 860. This changes the amino acid from a serine to a stop codon within coding exon 8. This alteration has been reported as a de novo finding in a patient with macrocephaly (Lee H et al. JAMA, 2014 Nov;312:1880-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Bannayan-Riley-Ruvalcaba syndrome;C1854416:Macrocephaly-autism syndrome;CN072330:Cowden syndrome 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | UCLA Clinical Genomics Center, UCLA | Jul 30, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at