11-108271228-CTTTTT-CTTTT

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.2922-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 142,066 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 0.0056 ( 0 hom., cov: 31)

Exomes 𝑓: 0.38 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ATM
NM_000051.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

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):

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 -8 ACMG points.

BP6

Variant 11-108271228-CT-C is Benign according to our data. Variant chr11-108271228-CT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 490504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.2922-8delT		splice_region intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.2922-8delT		splice_region intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.2922-22delT	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.2922-22delT	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.2922-22delT	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.00554

AC:

787

AN:

142030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00663

Gnomad AMI

AF:

0.00342

Gnomad AMR

AF:

0.00273

Gnomad ASJ

AF:

0.00243

Gnomad EAS

AF:

0.00386

Gnomad SAS

AF:

0.000449

Gnomad FIN

AF:

0.0214

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00417

Gnomad OTH

AF:

0.00309

GnomAD2 exomes

AF:

0.436

AC:

81177

AN:

186328

AF XY:

0.444

show subpopulations

Gnomad AFR exome

AF:

0.405

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.450

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.376

AC:

365161

AN:

971484

Hom.:

Cov.:

AF XY:

0.382

AC XY:

186052

AN XY:

486914

show subpopulations

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

African (AFR)

AF:

0.337

AC:

8042

AN:

23860

American (AMR)

AF:

0.291

AC:

10635

AN:

36520

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

7890

AN:

18876

East Asian (EAS)

AF:

0.418

AC:

12103

AN:

28942

South Asian (SAS)

AF:

0.428

AC:

27003

AN:

63136

European-Finnish (FIN)

AF:

0.395

AC:

15265

AN:

38684

Middle Eastern (MID)

AF:

0.367

AC:

1365

AN:

3716

European-Non Finnish (NFE)

AF:

0.373

AC:

267237

AN:

716558

Other (OTH)

AF:

0.379

AC:

15621

AN:

41192

⚠️ 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: 0.258

Heterozygous variant carriers

43578

87156

130735

174313

217891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9144

18288

27432

36576

45720

<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:

0.00559

AC:

794

AN:

142066

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

445

AN XY:

68924

show subpopulations

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

African (AFR)

AF:

0.00677

AC:

264

AN:

38982

American (AMR)

AF:

0.00273

AC:

AN:

14294

Ashkenazi Jewish (ASJ)

AF:

0.00243

AC:

AN:

3298

East Asian (EAS)

AF:

0.00387

AC:

AN:

4908

South Asian (SAS)

AF:

0.000226

AC:

AN:

4426

European-Finnish (FIN)

AF:

0.0214

AC:

183

AN:

8542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00419

AC:

270

AN:

64512

Other (OTH)

AF:

0.00359

AC:

AN:

1952

⚠️ 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: 0.349

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.158

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Hereditary cancer-predisposing syndrome (2)

not provided (2)

Ataxia-telangiectasia syndrome (1)

Breast and/or ovarian cancer (1)

Computational scores

Source: dbNSFP v4.9

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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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