rs397516793
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_002755.4(MAP2K1):c.388T>A(p.Tyr130Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y130C) has been classified as Pathogenic.
Frequency
Consequence
NM_002755.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K1 | NM_002755.4 | c.388T>A | p.Tyr130Asn | missense_variant | 3/11 | ENST00000307102.10 | |
MAP2K1 | NM_001411065.1 | c.322T>A | p.Tyr108Asn | missense_variant | 3/10 | ||
MAP2K1 | XM_011521783.4 | c.322T>A | p.Tyr108Asn | missense_variant | 3/11 | ||
MAP2K1 | XM_017022411.3 | c.388T>A | p.Tyr130Asn | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K1 | ENST00000307102.10 | c.388T>A | p.Tyr130Asn | missense_variant | 3/11 | 1 | NM_002755.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cardiofaciocutaneous syndrome 3 Pathogenic:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - CFC International | - | Variant interpreted as Pathogenic and reported on 09-28-2018 by Lab or GTR ID 1006. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. - |
Pathogenic, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Jul 13, 2018 | A mosaic de novo c.388T>A (p.Y130N) pathogenic variant in the MAP2K1 gene was detected by exome sequencing and confirmed by Sanger sequencing. The c.388T>A (p.Y130N) variant has been previously reported as disease-causing in one patient with cardiofaciocutaneous syndrome [PMID 18413255] and is absent in the general population (gnomAD database). In addition, allelic variants of c.389A>G (p.Y130C) and c.388T>C (p.Y130H) are both pathogenic variants previously reported in multiple affected patients. Functional studies showed protein with p.Y130C variant has increased kinase activity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at