2-25234321-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_022552.5(DNMT3A):c.2697C>T(p.Arg899=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,614,096 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 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
DNMT3A
NM_022552.5 synonymous
NM_022552.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.17
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 2-25234321-G-A is Benign according to our data. Variant chr2-25234321-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 728368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT3A | NM_022552.5 | c.2697C>T | p.Arg899= | synonymous_variant | 23/23 | ENST00000321117.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3A | ENST00000321117.10 | c.2697C>T | p.Arg899= | synonymous_variant | 23/23 | 1 | NM_022552.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152226Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000263 AC: 66AN: 251350Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135840
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GnomAD4 exome AF: 0.000150 AC: 219AN: 1461752Hom.: 0 Cov.: 31 AF XY: 0.000150 AC XY: 109AN XY: 727170
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | DNMT3A: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2021 | This variant is associated with the following publications: (PMID: 22744846) - |
Tatton-Brown-Rahman overgrowth syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at