2-175105857-A-C

Position:

• chr2-175105857-A-C

Variant summary

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

The NM_001880.4(ATF2):​c.828+5711T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 152,290 control chromosomes in the GnomAD database, including 192 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 0.033 (192 hom., cov: 32)
• Consequence: ATF2 NM_001880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF2	NM_001880.4	c.828+5711T>G		intron_variant		ENST00000264110.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF2	ENST00000264110.7	c.828+5711T>G		intron_variant		1	NM_001880.4

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5017 AN: 152170 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00713

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0330 AC: 5033 AN: 152290 Hom.: 192 Cov.: 32 AF XY: 0.0327 AC XY: 2434 AN XY: 74486

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0333

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00713

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0227 Hom.: 13

Bravo AF: 0.0388

Asia WGS AF: 0.0150 AC: 50 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.7
DANN	Benign	0.70

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: rs1153679; hg19: chr2-175970585;