chr15-66443272-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002755.4(MAP2K1):c.439-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 1,584,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_002755.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K1 | NM_002755.4 | c.439-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000307102.10 | |||
MAP2K1 | NM_001411065.1 | c.373-1384G>A | intron_variant | ||||
MAP2K1 | XM_011521783.4 | c.373-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
MAP2K1 | XM_017022411.3 | c.439-1384G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K1 | ENST00000307102.10 | c.439-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002755.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151946Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251406Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135890
GnomAD4 exome AF: 0.0000293 AC: 42AN: 1432562Hom.: 0 Cov.: 28 AF XY: 0.0000238 AC XY: 17AN XY: 714692
GnomAD4 genome AF: 0.0000395 AC: 6AN: 151946Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74212
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 25, 2015 | c.439-8G>A in intron 3 of MAP2K1: 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 MAP2K1-associated Noonan syndrome. It has been identified in 4/66606 European chromosomes by the Exome Ag gregation Consortium (ExAC, http://exac.broadinstitute.org). - |
MAP2K1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 15, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at