rs2066734

Variant names:

• chr11-108227732-TAA-T
• rs2066734
• NM_000051.4:c.72+37_72+38delAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000051.4(ATM):​c.72+37_72+38delAA 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.268

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.72+37_72+38delAA		intron_variant	Intron 2 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.72+37_72+38delAA		intron_variant	Intron 2 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55042 AN: 151744 Hom.: 11200 Cov.: 0

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

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

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.: 0 AF XY: 0.370 AC XY: 27447 AN XY: 74208

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

Submissions by phenotype

not specified Benign:4

Nov 12, 2023

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 70% of patients studied by a panel of primary immunodeficiencies. Number of patients: 67. Only high quality variants are reported. -

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Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary breast ovarian cancer syndrome Benign:1

Apr 19, 2022

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs2066734; hg19: chr11-108098459; COSMIC: COSV53723852; COSMIC: COSV53723852;