rs10497434

Positions:

• chr2-175151112-T-C

Variant summary

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

The NM_001880.4(ATF2):​c.-96A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,532 control chromosomes in the GnomAD database, including 1,215 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 0.11 (1214 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1 hom.)
• Consequence: ATF2 NM_001880.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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]

ATF2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF2	NM_001880.4	c.-96A>G		5_prime_UTR_premature_start_codon_gain_variant	2/14	ENST00000264110.7	NP_001871.2
ATF2	NM_001880.4	c.-96A>G		5_prime_UTR_variant	2/14	ENST00000264110.7	NP_001871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF2	ENST00000264110.7	c.-96A>G		5_prime_UTR_premature_start_codon_gain_variant	2/14	1	NM_001880.4	ENSP00000264110.2
ATF2	ENST00000264110.7	c.-96A>G		5_prime_UTR_variant	2/14	1	NM_001880.4	ENSP00000264110.2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16575 AN: 151994 Hom.: 1210 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0786

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0866

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.0993

GnomAD4 exome AF: 0.0333 AC: 14 AN: 420 Hom.: 1 Cov.: 0 AF XY: 0.0320 AC XY: 8 AN XY: 250

Gnomad4 FIN exome AF: 0.0338

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.109 AC: 16607 AN: 152112 Hom.: 1214 Cov.: 32 AF XY: 0.108 AC XY: 8014 AN XY: 74362

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.0834

Gnomad4 ASJ AF: 0.0786

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0858

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.0983

Alfa AF: 0.0768 Hom.: 898

Bravo AF: 0.117

Asia WGS AF: 0.126 AC: 439 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10497434; hg19: chr2-176015840;