rs672655

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000051.4(ATM):c.2377-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,410,390 control chromosomes in the GnomAD database, including 217,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20115 hom., cov: 32)

Exomes 𝑓: 0.56 ( 197198 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.18

Publications

25 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

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 11-108258930-A-G is Benign according to our data. Variant chr11-108258930-A-G is described in ClinVar as Benign. ClinVar VariationId is 1177614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 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.2377-56A>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.2377-56A>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.2377-56A>G	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.2377-56A>G	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.2377-56A>G	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75137

AN:

151940

Hom.:

20105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.607

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.538

GnomAD4 exome

AF:

0.556

AC:

699635

AN:

1258332

Hom.:

197198

AF XY:

0.560

AC XY:

355690

AN XY:

635680

show subpopulations

African (AFR)

AF:

0.268

AC:

7912

AN:

29520

American (AMR)

AF:

0.629

AC:

27221

AN:

43278

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

15130

AN:

24720

East Asian (EAS)

AF:

0.430

AC:

16587

AN:

38534

South Asian (SAS)

AF:

0.597

AC:

48513

AN:

81196

European-Finnish (FIN)

AF:

0.627

AC:

32258

AN:

51488

Middle Eastern (MID)

AF:

0.715

AC:

3795

AN:

5306

European-Non Finnish (NFE)

AF:

0.557

AC:

518891

AN:

930824

Other (OTH)

AF:

0.549

AC:

29328

AN:

53466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

15941

31882

47823

63764

79705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13436

26872

40308

53744

67180

<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:

0.494

AC:

75167

AN:

152058

Hom.:

20115

Cov.:

AF XY:

0.503

AC XY:

37388

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.276

AC:

11446

AN:

41480

American (AMR)

AF:

0.607

AC:

9260

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

2220

AN:

3468

East Asian (EAS)

AF:

0.421

AC:

2179

AN:

5180

South Asian (SAS)

AF:

0.604

AC:

2912

AN:

4822

European-Finnish (FIN)

AF:

0.629

AC:

6641

AN:

10562

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38556

AN:

67970

Other (OTH)

AF:

0.539

AC:

1139

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1810

3619

5429

7238

9048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.503

Hom.:

3022

Bravo

AF:

0.481

Asia WGS

AF:

0.531

AC:

1844

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Ataxia-telangiectasia syndrome (1)

Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

2.2

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

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