rs2300582

Variant names:

• chr2-175088353-T-C
• rs2300582
• NM_001880.4:c.1185+4708A>G

Variant summary

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

The NM_001880.4(ATF2):​c.1185+4708A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 152,194 control chromosomes in the GnomAD database, including 369 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 0.069 (369 hom., cov: 32)
• Consequence: ATF2 NM_001880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• Publications: 1 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF2	NM_001880.4	c.1185+4708A>G		intron_variant	Intron 12 of 13	ENST00000264110.7	NP_001871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF2	ENST00000264110.7	c.1185+4708A>G		intron_variant	Intron 12 of 13	1	NM_001880.4	ENSP00000264110.2

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10516 AN: 152076 Hom.: 369 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0858

Gnomad FIN AF: 0.0430

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.0724

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

GnomAD4 genome AF: 0.0691 AC: 10524 AN: 152194 Hom.: 369 Cov.: 32 AF XY: 0.0690 AC XY: 5135 AN XY: 74410

African (AFR) AF: 0.0717 AC: 2978 AN: 41530

American (AMR) AF: 0.0683 AC: 1045 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.128 AC: 660 AN: 5162

South Asian (SAS) AF: 0.0854 AC: 411 AN: 4812

European-Finnish (FIN) AF: 0.0430 AC: 456 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0665 AC: 4520 AN: 67996

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.0660 Hom.: 51

Bravo AF: 0.0707

Asia WGS AF: 0.119 AC: 415 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		0.57
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: rs2300582; hg19: chr2-175953081;