3-142553915-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001184.4(ATR):c.2442A>G(p.Glu814Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 1,612,650 control chromosomes in the GnomAD database, including 866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 436 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 430 hom. )

Consequence

ATR
NM_001184.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.44

Publications

4 publications found

Variant links:

COSMIC-nc: COSV104670823

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 Gene-Disease associations (from GenCC):

Seckel syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Ambry Genetics
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome
Inheritance: Unknown, AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
familial prostate carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-142553915-T-C is Benign according to our data. Variant chr3-142553915-T-C is described in ClinVar as Benign. ClinVar VariationId is 157971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	NM_001184.4	MANE Select	c.2442A>G	p.Glu814Glu	synonymous	Exon 11 of 47	NP_001175.2
	ATR	NM_001354579.2		c.2250A>G	p.Glu750Glu	synonymous	Exon 10 of 46	NP_001341508.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATR	ENST00000350721.9	TSL:1 MANE Select	c.2442A>G	p.Glu814Glu	synonymous	Exon 11 of 47	ENSP00000343741.4
ATR	ENST00000661310.1		c.2250A>G	p.Glu750Glu	synonymous	Exon 10 of 46	ENSP00000499589.1
ATR	ENST00000515149.3	TSL:3	n.*1216A>G		non_coding_transcript_exon	Exon 10 of 18	ENSP00000425897.3

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6331

AN:

152158

Hom.:

436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0273

GnomAD2 exomes

AF:

0.0110

AC:

2767

AN:

250450

AF XY:

0.00772

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.00624

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00558

GnomAD4 exome

AF:

0.00432

AC:

6304

AN:

1460374

Hom.:

430

Cov.:

AF XY:

0.00370

AC XY:

2688

AN XY:

726530

show subpopulations

African (AFR)

AF:

0.154

AC:

5151

AN:

33406

American (AMR)

AF:

0.00728

AC:

325

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26096

East Asian (EAS)

AF:

0.000101

AC:

AN:

39556

South Asian (SAS)

AF:

0.000267

AC:

AN:

86056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00435

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.000224

AC:

249

AN:

1111140

Other (OTH)

AF:

0.00872

AC:

526

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

313

626

938

1251

1564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0416

AC:

6337

AN:

152276

Hom.:

436

Cov.:

AF XY:

0.0394

AC XY:

2936

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.145

AC:

6014

AN:

41524

American (AMR)

AF:

0.0142

AC:

217

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68028

Other (OTH)

AF:

0.0270

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

283

566

849

1132

1415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0217

Hom.:

124

Bravo

AF:

0.0486

Asia WGS

AF:

0.00811

AC:

AN:

3468

EpiCase

AF:

0.000109

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome (2)

Seckel syndrome 1 (2)

ATR-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.9

(source)

DANN

Benign

0.56

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over