rs79402775

Positions:

• chr2-175167648-G-A
• chr2-175167648-G-T

Variant summary

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

The NM_001880.4(ATF2):​c.-143+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 500,784 control chromosomes in the GnomAD database, including 870 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 0.030 (179 hom., cov: 32)
  • Exomes 𝑓: 0.043 (691 hom.)
• Consequence: ATF2 NM_001880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742

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]

MIR933 (HGNC:33676): (microRNA 933) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF2	NM_001880.4	c.-143+402C>T		intron_variant		ENST00000264110.7
MIR933	NR_030630.1	n.62C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF2	ENST00000264110.7	c.-143+402C>T		intron_variant		1	NM_001880.4
MIR933	ENST00000401154.1	n.62C>T		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4552 AN: 152120 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.0443 AC: 8654 AN: 195532 Hom.: 418 AF XY: 0.0495 AC XY: 5206 AN XY: 105278

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.00885

Gnomad ASJ exome AF: 0.0364

Gnomad EAS exome AF: 0.156

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.0482

Gnomad NFE exome AF: 0.0217

Gnomad OTH exome AF: 0.0361

GnomAD4 exome AF: 0.0429 AC: 14952 AN: 348546 Hom.: 691 Cov.: 0 AF XY: 0.0499 AC XY: 9866 AN XY: 197656

Gnomad4 AFR exome AF: 0.0158

Gnomad4 AMR exome AF: 0.00867

Gnomad4 ASJ exome AF: 0.0370

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0464

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0334

GnomAD4 genome AF: 0.0299 AC: 4548 AN: 152238 Hom.: 179 Cov.: 32 AF XY: 0.0339 AC XY: 2526 AN XY: 74428

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0997

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0209

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0165 Hom.: 13

Bravo AF: 0.0246

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs79402775; hg19: chr2-176032376; COSMIC: COSV51373662; COSMIC: COSV51373662;