chr12-112454556-C-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.526-8C>A variant in the PTPN11 gene is 0.079% (65/66646) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) LINK:https://erepo.genome.network/evrepo/ui/classification/CA134672/MONDO:0021060/004
Frequency
Consequence
NM_002834.5 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPN11 | ENST00000351677.7 | c.526-8C>A | splice_region_variant, intron_variant | Intron 4 of 15 | 1 | NM_002834.5 | ENSP00000340944.3 | |||
PTPN11 | ENST00000635625.1 | c.526-8C>A | splice_region_variant, intron_variant | Intron 4 of 14 | 5 | ENSP00000489597.1 |
Frequencies
GnomAD3 genomes AF: 0.000605 AC: 92AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000670 AC: 168AN: 250918Hom.: 1 AF XY: 0.000568 AC XY: 77AN XY: 135610
GnomAD4 exome AF: 0.00138 AC: 1986AN: 1443530Hom.: 4 Cov.: 30 AF XY: 0.00135 AC XY: 973AN XY: 719330
GnomAD4 genome AF: 0.000604 AC: 92AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74454
ClinVar
Submissions by phenotype
not provided Benign:7
- -
- -
- -
- -
- -
PTPN11: BP4, BS1 -
- -
not specified Benign:5
c.526-8C>A in intron 4 of PTPN11: This variant is not expected to have clinical significance because a change at this position does not diverge from the splice consensus sequence and is therefore unlikely to impact splicing. Furthermore, sp lice variants are not a known mechanism of disease for Noonan syndrome. It has a lso been identified in 0.1% (65/66646) of European chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs184804143). -
- -
- -
- -
- -
RASopathy Benign:3
- -
- -
The filtering allele frequency of the c.526-8C>A variant in the PTPN11 gene is 0.079% (65/66646) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) -
LEOPARD syndrome 1 Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. -
Noonan syndrome 1 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Metachondromatosis Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Noonan syndrome Benign:1
- -
Noonan syndrome and Noonan-related syndrome Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at