rs587777506
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_022552.5(DNMT3A):c.889_891del(p.Trp297del) variant causes a inframe deletion 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
DNMT3A
NM_022552.5 inframe_deletion
NM_022552.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.22
Genes affected
DNMT3A (HGNC:2978): (DNA methyltransferase 3 alpha) CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_022552.5
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_022552.5. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 2-25247713-CCCA-C is Pathogenic according to our data. Variant chr2-25247713-CCCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 139615.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-25247713-CCCA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT3A | NM_022552.5 | c.889_891del | p.Trp297del | inframe_deletion | 8/23 | ENST00000321117.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3A | ENST00000321117.10 | c.889_891del | p.Trp297del | inframe_deletion | 8/23 | 1 | NM_022552.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Tatton-Brown-Rahman overgrowth syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at