chr2-175105857-A-C

Variant names:

• chr2-175105857-A-C
• rs1153679
• NM_001880.4:c.828+5711T>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.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
• Publications: 0 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=-0.82).
• 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 rank	MANE	Protein	UniProt
ATF2	NM_001880.4	c.828+5711T>G		intron_variant	Intron 10 of 13	ENST00000264110.7	NP_001871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF2	ENST00000264110.7	c.828+5711T>G		intron_variant	Intron 10 of 13	1	NM_001880.4	ENSP00000264110.2

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

African (AFR) AF: 0.0927 AC: 3852 AN: 41556

American (AMR) AF: 0.0231 AC: 353 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0333 AC: 161 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.00713 AC: 485 AN: 68020

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

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
PhyloP100		2.7
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: rs1153679; hg19: chr2-175970585;