chr2-175074807-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001880.4(ATF2):c.1320C>T(p.Asp440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,613,456 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0050 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 10 hom. )
Consequence
ATF2
NM_001880.4 synonymous
NM_001880.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.85
Genes affected
ATF2 (HGNC:784): (activating transcription factor 2) This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. It forms a homodimer or a heterodimer with c-Jun and stimulates CRE-dependent transcription. This protein is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in vitro; thus it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. The encoded protein may also be involved in cell's DNA damage response independent of its role in transcriptional regulation. Several alternatively spliced transcript variants have been found for this gene [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 2-175074807-G-A is Benign according to our data. Variant chr2-175074807-G-A is described in ClinVar as [Benign]. Clinvar id is 775788.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.85 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00501 (763/152268) while in subpopulation AFR AF= 0.0179 (742/41562). AF 95% confidence interval is 0.0168. There are 9 homozygotes in gnomad4. There are 360 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 760 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATF2 | NM_001880.4 | c.1320C>T | p.Asp440= | synonymous_variant | 14/14 | ENST00000264110.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATF2 | ENST00000264110.7 | c.1320C>T | p.Asp440= | synonymous_variant | 14/14 | 1 | NM_001880.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00500 AC: 760AN: 152150Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00137 AC: 341AN: 249130Hom.: 3 AF XY: 0.00101 AC XY: 136AN XY: 134816
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GnomAD4 exome AF: 0.000530 AC: 775AN: 1461188Hom.: 10 Cov.: 31 AF XY: 0.000453 AC XY: 329AN XY: 726892
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GnomAD4 genome ? AF: 0.00501 AC: 763AN: 152268Hom.: 9 Cov.: 32 AF XY: 0.00484 AC XY: 360AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 25, 2018 | - - |
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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at