rs201957261
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_002834.5(PTPN11):c.*13A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 1,549,058 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00047 ( 0 hom. )
Consequence
PTPN11
NM_002834.5 3_prime_UTR
NM_002834.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.522
Genes affected
PTPN11 (HGNC:9644): (protein tyrosine phosphatase non-receptor type 11) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant 12-112504777-A-G is Benign according to our data. Variant chr12-112504777-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 138844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-112504777-A-G is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd4 at 39 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN11 | NM_002834.5 | c.*13A>G | 3_prime_UTR_variant | 15/16 | ENST00000351677.7 | ||
PTPN11 | NM_001330437.2 | c.*13A>G | 3_prime_UTR_variant | 15/16 | |||
PTPN11 | NM_001374625.1 | c.*13A>G | 3_prime_UTR_variant | 15/16 | |||
PTPN11 | XM_011538613.3 | c.*13A>G | 3_prime_UTR_variant | 15/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN11 | ENST00000351677.7 | c.*13A>G | 3_prime_UTR_variant | 15/16 | 1 | NM_002834.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000256 AC: 39AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000332 AC: 83AN: 250256Hom.: 0 AF XY: 0.000318 AC XY: 43AN XY: 135298
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GnomAD4 exome AF: 0.000468 AC: 653AN: 1396734Hom.: 0 Cov.: 29 AF XY: 0.000482 AC XY: 336AN XY: 697766
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GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 07, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 13, 2015 | c.*13A>G in the 3'UTR of PTPN11: This variant is not expected to have clinical significance because it has been identified in 0.1% (43/62072) of European chrom osomes by the Exome Aggregation Constortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs201957261). - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 05, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at