NM_000051.4:c.72+37_72+38delAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000051.4(ATM):c.72+37_72+38delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,612,058 control chromosomes in the GnomAD database, including 142,105 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11205 hom., cov: 0)

Exomes 𝑓: 0.42 ( 130900 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.268

Publications

17 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):

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

ATM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 11-108227732-TAA-T is Benign according to our data. Variant chr11-108227732-TAA-T is described in ClinVar as Benign. ClinVar VariationId is 1178525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATM	NM_000051.4	MANE Select	c.72+37_72+38delAA	intron	N/A	NP_000042.3
ATM	NM_001351834.2		c.72+37_72+38delAA	intron	N/A	NP_001338763.1
ATM	NM_001351835.2		c.72+37_72+38delAA	intron	N/A	NP_001338764.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATM	ENST00000675843.1	MANE Select	c.72+37_72+38delAA	intron	N/A	ENSP00000501606.1
ATM	ENST00000452508.7	TSL:1	c.72+37_72+38delAA	intron	N/A	ENSP00000388058.2
ATM	ENST00000531525.3	TSL:1	c.72+37_72+38delAA	intron	N/A	ENSP00000434327.3

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55042

AN:

151744

Hom.:

11200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.415

GnomAD2 exomes

AF:

0.435

AC:

109355

AN:

251264

AF XY:

0.442

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.566

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.388

Gnomad FIN exome

AF:

0.387

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.419

AC:

611621

AN:

1460196

Hom.:

130900

AF XY:

0.423

AC XY:

307658

AN XY:

726560

show subpopulations

African (AFR)

AF:

0.167

AC:

5569

AN:

33422

American (AMR)

AF:

0.558

AC:

24931

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

12480

AN:

26108

East Asian (EAS)

AF:

0.397

AC:

15739

AN:

39596

South Asian (SAS)

AF:

0.519

AC:

44741

AN:

86208

European-Finnish (FIN)

AF:

0.389

AC:

20779

AN:

53404

Middle Eastern (MID)

AF:

0.587

AC:

3380

AN:

5754

European-Non Finnish (NFE)

AF:

0.413

AC:

458632

AN:

1110658

Other (OTH)

AF:

0.420

AC:

25370

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

19558

39116

58673

78231

97789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14050

28100

42150

56200

70250

<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:

0.363

AC:

55057

AN:

151862

Hom.:

11205

Cov.:

AF XY:

0.370

AC XY:

27447

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.172

AC:

7114

AN:

41478

American (AMR)

AF:

0.505

AC:

7709

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1719

AN:

3466

East Asian (EAS)

AF:

0.393

AC:

2030

AN:

5170

South Asian (SAS)

AF:

0.526

AC:

2529

AN:

4806

European-Finnish (FIN)

AF:

0.388

AC:

4076

AN:

10500

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.420

AC:

28533

AN:

67874

Other (OTH)

AF:

0.418

AC:

880

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1713

3427

5140

6854

8567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.406

Hom.:

2401

Bravo

AF:

0.360

Asia WGS

AF:

0.479

AC:

1662

AN:

3472

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Hereditary breast ovarian cancer syndrome (1)

Hereditary cancer-predisposing syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.27

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.20

Position offset: -36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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