11-108271228-CTTTTT-CTTTTTT

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.2922-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,516,430 control chromosomes in the GnomAD database, including 197 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 196 hom., cov: 31)

Exomes 𝑓: 0.030 ( 1 hom. )

Consequence

ATM
NM_000051.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.137

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 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 11-108271228-C-CT is Benign according to our data. Variant chr11-108271228-C-CT is described in ClinVar as [Benign]. Clinvar id is 1249532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4 link	c.2922-8dupT		splice_region_variant, intron_variant	Intron 19 of 62	ENST00000675843.1	NP_000042.3	Q13315A0A024R3C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1 link	c.2922-23_2922-22insT		intron_variant	Intron 19 of 62		NM_000051.4	ENSP00000501606.1		Q13315

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5148

AN:

142408

Hom.:

196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.00114

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.00574

Gnomad EAS

AF:

0.0164

Gnomad SAS

AF:

0.00225

Gnomad FIN

AF:

0.00634

Gnomad MID

AF:

0.00333

Gnomad NFE

AF:

0.00952

Gnomad OTH

AF:

0.0371

GnomAD2 exomes

AF:

0.0469

AC:

8737

AN:

186328

AF XY:

0.0391

show subpopulations

Gnomad AFR exome

AF:

0.0774

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.0269

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.0240

Gnomad OTH exome

AF:

0.0355

GnomAD4 exome

AF:

0.0302

AC:

41443

AN:

1373970

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

19204

AN XY:

685824

show subpopulations

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

African (AFR)

AF:

0.0694

AC:

2193

AN:

31608

American (AMR)

AF:

0.142

AC:

6074

AN:

42724

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

316

AN:

25384

East Asian (EAS)

AF:

0.0171

AC:

662

AN:

38772

South Asian (SAS)

AF:

0.0135

AC:

1127

AN:

83504

European-Finnish (FIN)

AF:

0.0137

AC:

680

AN:

49618

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

5204

European-Non Finnish (NFE)

AF:

0.0274

AC:

28446

AN:

1039678

Other (OTH)

AF:

0.0323

AC:

1859

AN:

57478

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.286

Heterozygous variant carriers

4020

8041

12061

16082

20102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0362

AC:

5156

AN:

142460

Hom.:

196

Cov.:

AF XY:

0.0368

AC XY:

2544

AN XY:

69172

show subpopulations

African (AFR)

AF:

0.0655

AC:

2555

AN:

39000

American (AMR)

AF:

0.122

AC:

1748

AN:

14326

Ashkenazi Jewish (ASJ)

AF:

0.00574

AC:

AN:

3308

East Asian (EAS)

AF:

0.0161

AC:

AN:

4912

South Asian (SAS)

AF:

0.00226

AC:

AN:

4430

European-Finnish (FIN)

AF:

0.00634

AC:

AN:

8678

Middle Eastern (MID)

AF:

0.00365

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00952

AC:

616

AN:

64696

Other (OTH)

AF:

0.0368

AC:

AN:

1958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

234

469

703

938

1172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0104

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 20, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: ATM c.2922-8dupT alters a nucleotide located close to a canonical splice site. The variant allele was found at a frequency of 0.047 in 186328 control chromosomes, predominantly at a frequency of 0.17 within the Latino subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 43.007 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATM causing Ataxia-Telangiectasia phenotype (0.004), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

not provided

Benign:1

Aug 30, 2019

GeneDx

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)

0.0

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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11-108271228-CTTTTT-CTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over