chr19-4102451-G-T
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_030662.4(MAP2K2):c.453C>A(p.Asp151Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. D151D) has been classified as Benign.
Frequency
Consequence
NM_030662.4 missense, splice_region
Scores
Clinical Significance
Conservation
Publications
- cardiofaciocutaneous syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- cardiofaciocutaneous syndrome 4Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- neurofibromatosis-Noonan syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Noonan syndromeInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAP2K2 | NM_030662.4 | c.453C>A | p.Asp151Glu | missense_variant, splice_region_variant | Exon 4 of 11 | ENST00000262948.10 | NP_109587.1 | |
MAP2K2 | NM_001440688.1 | c.453C>A | p.Asp151Glu | missense_variant, splice_region_variant | Exon 4 of 9 | NP_001427617.1 | ||
MAP2K2 | NM_001440689.1 | c.-118C>A | splice_region_variant | Exon 2 of 9 | NP_001427618.1 | |||
MAP2K2 | NM_001440689.1 | c.-118C>A | 5_prime_UTR_variant | Exon 2 of 9 | NP_001427618.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.92e-7 AC: 1AN: 1445374Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 717718 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at