chr19-4117530-GA-AG
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3
The NM_030662.4(MAP2K2):c.191_192delTCinsCT(p.Val64Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V64F) has been classified as Pathogenic.
Frequency
Consequence
NM_030662.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAP2K2 | ENST00000262948.10 | c.191_192delTCinsCT | p.Val64Ala | missense_variant | 1 | NM_030662.4 | ENSP00000262948.4 | |||
MAP2K2 | ENST00000394867.9 | n.630_631delTCinsCT | non_coding_transcript_exon_variant | Exon 1 of 10 | 5 | |||||
MAP2K2 | ENST00000599345.1 | n.388_389delTCinsCT | non_coding_transcript_exon_variant | Exon 2 of 7 | 5 | |||||
MAP2K2 | ENST00000687128.1 | n.630_631delTCinsCT | non_coding_transcript_exon_variant | Exon 1 of 7 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
The c.191_192delTCinsCT (p.V64A) alteration, located in exon 2 (coding exon 2) of the MAP2K2 gene, consists of an in-frame substitution of 2 nucleotides from position 191 to 192, causing the valine (V) at amino acid position 64 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
RASopathy Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 64 of the MAP2K2 protein (p.Val64Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MAP2K2-related conditions. ClinVar contains an entry for this variant (Variation ID: 543986). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at