11-108253759-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000051.4(ATM):c.1899-55T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,348,084 control chromosomes in the GnomAD database, including 1,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene ATM is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.030 ( 105 hom., cov: 32)

Exomes 𝑓: 0.039 ( 999 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.845

Publications

13 publications found

Variant links:

Genes affected

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

ATM Gene-Disease associations (from GenCC):

ATM-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
ataxia telangiectasia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Laboratory for Molecular Medicine
prostate cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
gastric carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATM links:

Genome browser will be placed here

ACMG classification

Specifications for ATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-108253759-T-G is Benign according to our data. Variant chr11-108253759-T-G is described in ClinVar as Benign. ClinVar VariationId is 453393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.1899-55T>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.1899-55T>G		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.1899-55T>G	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.1899-55T>G	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.1899-55T>G	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4608

AN:

152166

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00675

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.0501

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0379

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0464

Gnomad OTH

AF:

0.0296

GnomAD4 exome

AF:

0.0388

AC:

46347

AN:

1195800

Hom.:

999

AF XY:

0.0388

AC XY:

23601

AN XY:

607608

show subpopulations

African (AFR)

AF:

0.00632

AC:

176

AN:

27862

American (AMR)

AF:

0.0207

AC:

891

AN:

43092

Ashkenazi Jewish (ASJ)

AF:

0.0524

AC:

1273

AN:

24302

East Asian (EAS)

AF:

0.000131

AC:

AN:

38120

South Asian (SAS)

AF:

0.0299

AC:

2361

AN:

79004

European-Finnish (FIN)

AF:

0.0388

AC:

1818

AN:

46838

Middle Eastern (MID)

AF:

0.0679

AC:

338

AN:

4978

European-Non Finnish (NFE)

AF:

0.0426

AC:

37468

AN:

880000

Other (OTH)

AF:

0.0391

AC:

2017

AN:

51604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2172

4344

6516

8688

10860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1194

2388

3582

4776

5970

<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:

0.0303

AC:

4607

AN:

152284

Hom.:

105

Cov.:

AF XY:

0.0302

AC XY:

2249

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00673

AC:

280

AN:

41592

American (AMR)

AF:

0.0238

AC:

364

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

174

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5188

South Asian (SAS)

AF:

0.0284

AC:

137

AN:

4828

European-Finnish (FIN)

AF:

0.0379

AC:

402

AN:

10602

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0464

AC:

3152

AN:

67988

Other (OTH)

AF:

0.0298

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

237

475

712

950

1187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0413

Hom.:

227

Bravo

AF:

0.0273

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Ataxia-telangiectasia syndrome (2)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.62

(source)

DANN

Benign

0.51

PhyloP100

-0.84

Mutation Taster

=100/0

polymorphism

(source)

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

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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

Computational scores

Splicing

Publications

Other links and lift over