rs397516806
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM5PP2PP5BS2
The NM_002834.5(PTPN11):āc.661A>Gā(p.Ile221Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,457,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I221M) has been classified as Likely pathogenic.
Frequency
Consequence
NM_002834.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN11 | NM_002834.5 | c.661A>G | p.Ile221Val | missense_variant | 6/16 | ENST00000351677.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN11 | ENST00000351677.7 | c.661A>G | p.Ile221Val | missense_variant | 6/16 | 1 | NM_002834.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251318Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135834
GnomAD4 exome AF: 0.00000618 AC: 9AN: 1457014Hom.: 0 Cov.: 31 AF XY: 0.00000690 AC XY: 5AN XY: 725148
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | PTPN11: PM2, PP2, PP3, PS4:Supporting, BS4 - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 08, 2014 | The I221V missense mutation in the PTPN11 gene has been reported previously in association with Noonan syndrome (Lepri et al., 2014). The I221V mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The variant is found in NOONAN panel(s). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at