rs3755488

chr2-175079323-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001880.4(ATF2):c.1291+1337G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 152,070 control chromosomes in the GnomAD database, including 356 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 0.068 (356 hom., cov: 32)
• Consequence: ATF2 NM_001880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF2	NM_001880.4	c.1291+1337G>C		intron_variant		ENST00000264110.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF2	ENST00000264110.7	c.1291+1337G>C		intron_variant		1	NM_001880.4

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10318 AN: 151954 Hom.: 357 Cov.: 32

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0746

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0679 AC: 10325 AN: 152070 Hom.: 356 Cov.: 32 AF XY: 0.0677 AC XY: 5030 AN XY: 74328

Gnomad4 AFR AF: 0.0718

Gnomad4 AMR AF: 0.0664

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0644 Hom.: 43

Bravo AF: 0.0694

Asia WGS AF: 0.107 AC: 370 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	4.6
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs3755488; hg19: chr2-175944051;