Variant rs2066734 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000051.4(ATM):c.72+37_72+38del 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:6

Conservation

PhyloP100: -0.268

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1178525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108227732-TAA-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATM	NM_000051.4 linkuse as main transcript	c.72+37_72+38del		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1 linkuse as main transcript	c.72+37_72+38del		intron_variant			NM_000051.4	P1

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

GnomAD3 exomes

AF:

0.435

AC:

109355

AN:

251264

Hom.:

25210

AF XY:

0.442

AC XY:

60011

AN XY:

135832

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 SAS exome

AF:

0.517

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

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.558

Gnomad4 ASJ exome

AF:

0.478

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.363

AC:

55057

AN:

151862

Hom.:

11205

Cov.:

AF XY:

0.370

AC XY:

27447

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.496

Gnomad4 EAS

AF:

0.393

Gnomad4 SAS

AF:

0.526

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.420

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.406

Hom.:

2401

Bravo

AF:

0.360

Asia WGS

AF:

0.479

AC:

1662

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 70% of patients studied by a panel of primary immunodeficiencies. Number of patients: 67. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over