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GeneBe

2-175093202-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001880.4(ATF2):c.1044C>T(p.Asn348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000969 in 1,613,978 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00055 ( 10 hom. )

Consequence

ATF2
NM_001880.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.775
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-175093202-G-A is Benign according to our data. Variant chr2-175093202-G-A is described in ClinVar as [Benign]. Clinvar id is 775789.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.775 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00501 (762/152154) while in subpopulation AFR AF= 0.0179 (742/41518). AF 95% confidence interval is 0.0168. There are 9 homozygotes in gnomad4. There are 359 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 759 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATF2NM_001880.4 linkuse as main transcriptc.1044C>T p.Asn348= synonymous_variant 12/14 ENST00000264110.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATF2ENST00000264110.7 linkuse as main transcriptc.1044C>T p.Asn348= synonymous_variant 12/141 NM_001880.4 P15336-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00499
AC:
759
AN:
152036
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0179
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00137
AC:
343
AN:
251226
Hom.:
3
AF XY:
0.00102
AC XY:
138
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.0183
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000549
AC:
802
AN:
1461824
Hom.:
10
Cov.:
31
AF XY:
0.000470
AC XY:
342
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.0193
Gnomad4 AMR exome
AF:
0.00116
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.00101
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00501
AC:
762
AN:
152154
Hom.:
9
Cov.:
32
AF XY:
0.00483
AC XY:
359
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0179
Gnomad4 AMR
AF:
0.000851
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00281
Hom.:
1
Bravo
AF:
0.00592

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
9.2
Dann
Benign
0.64
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61740493; hg19: chr2-175957930; API