19-4110634-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000262948.10(MAP2K2):c.325C>G(p.Pro109Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P109L) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000262948.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAP2K2 | NM_030662.4 | c.325C>G | p.Pro109Ala | missense_variant | 3/11 | ENST00000262948.10 | NP_109587.1 | |
MAP2K2 | XM_006722799.3 | c.325C>G | p.Pro109Ala | missense_variant | 3/9 | XP_006722862.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAP2K2 | ENST00000262948.10 | c.325C>G | p.Pro109Ala | missense_variant | 3/11 | 1 | NM_030662.4 | ENSP00000262948 | P1 | |
MAP2K2 | ENST00000394867.9 | n.764C>G | non_coding_transcript_exon_variant | 2/10 | 5 | |||||
MAP2K2 | ENST00000599345.1 | n.522C>G | non_coding_transcript_exon_variant | 3/7 | 5 | |||||
MAP2K2 | ENST00000687128.1 | n.764C>G | non_coding_transcript_exon_variant | 2/7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250222Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135386
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460970Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726720
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
RASopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 16, 2016 | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MAP2K2-related disease. This sequence change replaces proline with alanine at codon 109 of the MAP2K2 protein (p.Pro109Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. - |
Noonan syndrome Benign:1
Likely benign, no assertion criteria provided | clinical testing | Service de Génétique Moléculaire, Hôpital Robert Debré | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at