Variant chr2-175167648-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001880.4(ATF2):c.-143+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 500,784 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.030 ( 179 hom., cov: 32)

Exomes 𝑓: 0.043 ( 691 hom. )

Consequence

ATF2
NM_001880.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.742

Variant links:

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]

ATF2 links:

MIR933 (HGNC:33676): (microRNA 933) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR933 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF2	NM_001880.4 linkuse as main transcript	c.-143+402C>T		intron_variant		ENST00000264110.7
MIR933	NR_030630.1 linkuse as main transcript	n.62C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF2	ENST00000264110.7 linkuse as main transcript	c.-143+402C>T		intron_variant		1	NM_001880.4		P15336-1
MIR933	ENST00000401154.1 linkuse as main transcript	n.62C>T		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4552

AN:

152120

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.0282

GnomAD3 exomes

AF:

0.0443

AC:

8654

AN:

195532

Hom.:

418

AF XY:

0.0495

AC XY:

5206

AN XY:

105278

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.00885

Gnomad ASJ exome

AF:

0.0364

Gnomad EAS exome

AF:

0.156

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0482

Gnomad NFE exome

AF:

0.0217

Gnomad OTH exome

AF:

0.0361

GnomAD4 exome

AF:

0.0429

AC:

14952

AN:

348546

Hom.:

691

Cov.:

AF XY:

0.0499

AC XY:

9866

AN XY:

197656

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.00867

Gnomad4 ASJ exome

AF:

0.0370

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.0464

Gnomad4 NFE exome

AF:

0.0206

Gnomad4 OTH exome

AF:

0.0334

GnomAD4 genome

AF:

0.0299

AC:

4548

AN:

152238

Hom.:

179

Cov.:

AF XY:

0.0339

AC XY:

2526

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.0334

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.0997

Gnomad4 FIN

AF:

0.0477

Gnomad4 NFE

AF:

0.0209

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0165

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.0970

AC:

337

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.2

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over