11-108271228-CTTTTT-CTTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000051.4(ATM):c.2922-9_2922-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,485,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0054 ( 0 hom. )

Consequence

ATM
NM_000051.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.137

Publications

5 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 -8 ACMG points.

BP6

Variant 11-108271228-CTT-C is Benign according to our data. Variant chr11-108271228-CTT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1802800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4 link	c.2922-9_2922-8delTT		splice_region_variant, intron_variant	Intron 19 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1 link	c.2922-22_2922-21delTT		intron_variant	Intron 19 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes

AF:

0.000288

AC:

AN:

142240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000771

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000140

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00256

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000201

Gnomad OTH

AF:

0.000515

GnomAD2 exomes

AF:

0.0153

AC:

2845

AN:

186328

AF XY:

0.0155

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.0133

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.00545

AC:

7314

AN:

1342764

Hom.:

AF XY:

0.00546

AC XY:

3656

AN XY:

670018

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00688

AC:

213

AN:

30980

American (AMR)

AF:

0.00925

AC:

388

AN:

41936

Ashkenazi Jewish (ASJ)

AF:

0.00764

AC:

187

AN:

24474

East Asian (EAS)

AF:

0.00631

AC:

234

AN:

37106

South Asian (SAS)

AF:

0.00709

AC:

576

AN:

81212

European-Finnish (FIN)

AF:

0.0115

AC:

544

AN:

47462

Middle Eastern (MID)

AF:

0.00782

AC:

AN:

5112

European-Non Finnish (NFE)

AF:

0.00470

AC:

4789

AN:

1018698

Other (OTH)

AF:

0.00615

AC:

343

AN:

55784

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.239

Heterozygous variant carriers

1243

2486

3730

4973

6216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

144

288

432

576

720

<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:

0.000288

AC:

AN:

142290

Hom.:

Cov.:

AF XY:

0.000275

AC XY:

AN XY:

69080

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000769

AC:

AN:

39004

American (AMR)

AF:

0.000140

AC:

AN:

14300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3306

East Asian (EAS)

AF:

0.00

AC:

AN:

4914

South Asian (SAS)

AF:

0.00

AC:

AN:

4426

European-Finnish (FIN)

AF:

0.00256

AC:

AN:

8600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.000201

AC:

AN:

64634

Other (OTH)

AF:

0.000511

AC:

AN:

1956

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.255

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0129

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breast and/or ovarian cancer

Benign:1

Jun 22, 2021

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over