2-175078526-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF2	NM_001880.4	c.1291+2134G>A		intron_variant	Intron 13 of 13	ENST00000264110.7	NP_001871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF2	ENST00000264110.7	c.1291+2134G>A		intron_variant	Intron 13 of 13	1	NM_001880.4	ENSP00000264110.2

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

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.926

Gnomad4 NFE AF: 0.877

Gnomad4 OTH AF: 0.771

Alfa AF: 0.794 Hom.: 6559

Bravo AF: 0.741

Asia WGS AF: 0.748 AC: 2601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.71

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: rs3845744; hg19: chr2-175943254;