rs2227929

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001184.4(ATR):c.1815T>C(p.Asp605=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,611,750 control chromosomes in the GnomAD database, including 120,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9172 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111042 hom. )

Consequence

ATR
NM_001184.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.576

Variant links:

Genes affected

ATR (HGNC:882): (ATR serine/threonine kinase) The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]

ATR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-142558694-A-G is Benign according to our data. Variant chr3-142558694-A-G is described in ClinVar as [Benign]. Clinvar id is 157966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-142558694-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.576 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATR	NM_001184.4 linkuse as main transcript	c.1815T>C	p.Asp605=	synonymous_variant	8/47	ENST00000350721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000350721.9 linkuse as main transcript	c.1815T>C	p.Asp605=	synonymous_variant	8/47	1	NM_001184.4	P1	Q13535-1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51293

AN:

151946

Hom.:

9167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.354

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.370

GnomAD3 exomes

AF:

0.357

AC:

89555

AN:

251068

Hom.:

16681

AF XY:

0.359

AC XY:

48721

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.386

AC:

563455

AN:

1459686

Hom.:

111042

Cov.:

AF XY:

0.384

AC XY:

278971

AN XY:

726228

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.322

Gnomad4 ASJ exome

AF:

0.450

Gnomad4 EAS exome

AF:

0.325

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.377

Gnomad4 NFE exome

AF:

0.405

Gnomad4 OTH exome

AF:

0.379

GnomAD4 genome

AF:

0.337

AC:

51316

AN:

152064

Hom.:

9172

Cov.:

AF XY:

0.337

AC XY:

25075

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.442

Gnomad4 EAS

AF:

0.354

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.372

Gnomad4 NFE

AF:

0.405

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.387

Hom.:

8361

Bravo

AF:

0.334

Asia WGS

AF:

0.322

AC:

1118

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 20, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 02, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -

Seckel syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

7.6

Dann

Benign

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over