chr2-175078526-C-T

Variant names:

• chr2-175078526-C-T
• rs3845744
• NM_001880.4:c.1291+2134G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001880.4(ATF2):​c.1291+2134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,158 control chromosomes in the GnomAD database, including 46,254 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 0.76 (46254 hom., cov: 32)
• Consequence: ATF2 NM_001880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001880.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF2	NM_001880.4	MANE Select	c.1291+2134G>A		intron	N/A	NP_001871.2
	ATF2	NM_001256090.2		c.1291+2134G>A		intron	N/A	NP_001243019.1
	ATF2	NM_001256091.2		c.1237+2134G>A		intron	N/A	NP_001243020.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF2	ENST00000264110.7	TSL:1 MANE Select	c.1291+2134G>A		intron	N/A	ENSP00000264110.2
	ATF2	ENST00000392544.5	TSL:1	c.1291+2134G>A		intron	N/A	ENSP00000376327.1
	ATF2	ENST00000426833.7	TSL:1	c.1237+2134G>A		intron	N/A	ENSP00000407911.3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115726 AN: 152040 Hom.: 46247 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.770

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.761 AC: 115766 AN: 152158 Hom.: 46254 Cov.: 32 AF XY: 0.764 AC XY: 56820 AN XY: 74400

African (AFR) AF: 0.488 AC: 20229 AN: 41468

American (AMR) AF: 0.835 AC: 12745 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2977 AN: 3472

East Asian (EAS) AF: 0.786 AC: 4072 AN: 5180

South Asian (SAS) AF: 0.744 AC: 3590 AN: 4826

European-Finnish (FIN) AF: 0.926 AC: 9830 AN: 10620

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59637 AN: 68010

Other (OTH) AF: 0.771 AC: 1625 AN: 2108

Alfa AF: 0.809 Hom.: 22394

Bravo AF: 0.741

Asia WGS AF: 0.748 AC: 2601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.71
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3845744; hg19: chr2-175943254;