rs143019052
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_002755.4(MAP2K1):c.957C>T(p.Asn319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
MAP2K1
NM_002755.4 synonymous
NM_002755.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.378
Genes affected
MAP2K1 (HGNC:6840): (mitogen-activated protein kinase kinase 1) The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 15-66487289-C-T is Benign according to our data. Variant chr15-66487289-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 50934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.378 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000526 (8/152184) while in subpopulation AFR AF= 0.000121 (5/41426). AF 95% confidence interval is 0.0000474. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K1 | NM_002755.4 | c.957C>T | p.Asn319= | synonymous_variant | 8/11 | ENST00000307102.10 | |
MAP2K1 | NM_001411065.1 | c.813C>T | p.Asn271= | synonymous_variant | 7/10 | ||
MAP2K1 | XM_011521783.4 | c.891C>T | p.Asn297= | synonymous_variant | 8/11 | ||
MAP2K1 | XM_017022411.3 | c.879C>T | p.Asn293= | synonymous_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K1 | ENST00000307102.10 | c.957C>T | p.Asn319= | synonymous_variant | 8/11 | 1 | NM_002755.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251484Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135920
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727182
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74360
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | Asn319Asn in exon 08 of MAP2K1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and it is not located within the splice consensus sequence. It has been identified in 1/8598 European American chromosomes from a broad population by the NHLBI Exome Sequencing Proj ect (http://evs.gs.washington.edu/EVS; dbSNP rs143019052). - |
MAP2K1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 30, 2019 | 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
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 03, 2021 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 12, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at