rs1153689

Positions:

• chr2-175083820-C-A
• chr2-175083820-C-T

Variant summary

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

The NM_001880.4(ATF2):​c.1186-3055G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,800 control chromosomes in the GnomAD database, including 6,154 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 0.26 (6154 hom., cov: 32)
• Consequence: ATF2 NM_001880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF2	NM_001880.4	c.1186-3055G>T		intron_variant		ENST00000264110.7	NP_001871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF2	ENST00000264110.7	c.1186-3055G>T		intron_variant		1	NM_001880.4	ENSP00000264110

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39605 AN: 151682 Hom.: 6129 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.261 AC: 39667 AN: 151800 Hom.: 6154 Cov.: 32 AF XY: 0.257 AC XY: 19083 AN XY: 74180

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.263

Alfa AF: 0.0945 Hom.: 108

Bravo AF: 0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.31
DANN	Benign	0.13

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: rs1153689; hg19: chr2-175948548;