rs751357509

Variant names:

• chr11-108251025-CAG-C
• rs587779817
• NM_000051.4:c.1564_1565delGA

Variant summary

Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1 PP5_Very_Strong

The NM_000051.4(ATM):​c.1564_1565delGA​(p.Glu522IlefsTer43) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000545 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: ATM NM_000051.4 frameshift
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:38 O:1
• Conservation: PhyloP100: 4.59

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 Pathogenic. Variant got 16 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 11-108251025-CAG-C is Pathogenic according to our data. Variant chr11-108251025-CAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 127340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108251025-CAG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.1564_1565delGA	p.Glu522IlefsTer43	frameshift_variant	Exon 10 of 63	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.1564_1565delGA	p.Glu522IlefsTer43	frameshift_variant	Exon 10 of 63		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000558 AC: 14 AN: 250850 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.0000547 AC: 80 AN: 1461862 Hom.: 0 AF XY: 0.0000454 AC XY: 33 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000710

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000491

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:38 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Pathogenic:13

Jul 31, 2024

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 04, 2024

Clinical Genetics Laboratory, Skane University Hospital Lund

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 12, 2023

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PVS1, PS4, PM2_SUP, PM3 -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATM: PM3:Very Strong, PVS1, PM2:Supporting -

-

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 18, 2020

Athena Diagnostics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. -

Aug 29, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 17, 2024

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The ATM c.1564_1565del (p.Glu522Ilefs*43) variant alters the translational reading frame of the ATM mRNA and causes the premature termination of ATM protein synthesis. This variant has been reported in the published literature in individuals affected with ataxia-telangiectasia (PMIDs: 30772474 (2019), 21965147 (2011), 10817650 (2000), 10330348 (1999)) and breast cancer (PMIDs: 29785153 (2018), 26681312 (2015)). The frequency of this variant in the general population, 0.00011 (12/113526 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. -

Mar 01, 2022

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in the heterozygous state in individuals with breast, pancreatic, and other cancers (Huang 2015, Hansford 2015, Mansfield 2016, Brand 2018, Dudley 2018, Waszak 2018, West 2018, Young 2018, Long 2019); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 1561_1562delAG, 1563_1564delAG, and 1562delAG; This variant is associated with the following publications: (PMID: 31447099, 29625052, 26689913, 28390840, 27533158, 29360161, 29753700, 28152038, 28843361, 31285527, 8789452, 21965147, 9792409, 23566627, 25980754, 22213089, 26506520, 11756177, 18634022, 26681312, 27083775, 28126470, 26182300, 27988859, 27479817, 28779002, 29785153, 28767289, 25186627, 30549301, 29445900, 30322717, 30612635, 31407689, 30772474, 30067863, 29945567, 29522266, 23242139, 31589614, 33436325, 32885271, 32427313, 32441320, 33098801, 33280026) -

Ataxia-telangiectasia syndrome Pathogenic:8

Mar 30, 2022

Genetics and Molecular Pathology, SA Pathology

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The ATM c.1564_1565del variant is classified as a PATHOGENIC variant (PVS1, PM2, PS4_supporting) The variant is a 2-base pair deletion in exon 10/63 of the ATM gene which results in a frameshift starting at codon Glutamic acid 522, changes this amino acid to an Isoleucine, and creating a premature STOP codon 43 amino acids downstream (denoted p.Glu522Ilefs*43) (PVS1). The variant has been reported in dbSNP (rs1374409941) but is rare in the disease databases (gnomAD: 8/152158, 0 homozygote) (PM2). The variant has been reported in both ClinVar (ID: #127340) and HGMD (accession: CD961794) as a disease causing variant (PS4_supporting). -

Oct 27, 2016

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jun 11, 2019

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 03, 2014

Counsyl

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: literature only

- -

Sep 16, 2020

Natera, Inc.

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 21, 2019

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Glu522Ilefs*43) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is present in population databases (rs751357509, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia and/or breast cancer (PMID: 9000145, 9463314, 10330348, 10817650, 12497634, 21965147, 27083775). This variant is also known as 1561delAG, 521ΔAG, 1563_1564delAG, 1563delAG, c.1564_1565delAG, and c.1561_1562delAG. For these reasons, this variant has been classified as Pathogenic. -

Jul 09, 2018

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

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: ATM c.1564_1565delGA (p.Glu522IlefsX43) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 5.3e-05 in 246034 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ATM causing Ataxia-Telangiectasia (5.3e-05 vs 0.004), allowing no conclusion about variant significance. The variant, c.1564_1565delGA, has been reported in the literature in multiple individuals affected with Ataxia-Telangiectasia (Demuth_2011, Stankovic_1998, Sandoval_199). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submission from clinical diagnostic laboratories (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -

Familial cancer of breast Pathogenic:7

Dec 09, 2022

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

PVS1, PM3_VSTR -

Mar 21, 2024

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2017

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This c.1564_1565del (p.Glu522Ilefs*43) has previously been reported a patient with ataxia telangiectasia [p.R521fs in PMID 8789452]. It has also been reported in patients with gastric cancer and suspected lynch syndrome [c.1561_1562del, p.R521fs in PMID 26506520]. This c.1564_1565del (p.Glu522Ilefs*43) variant been observed in 6 heterozygous individuals in the ExAC population database (http://exac.broadinstitute.org/variant/11-108121752-CAG-C). It is thus interpreted as a likely pathogenic variant. -

May 30, 2023

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 02, 2020

Department of Molecular Diagnostics, Institute of Oncology Ljubljana

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 23, 2022

MGZ Medical Genetics Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 17, 2024

Myriad Genetics, Inc.

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. -

Hereditary cancer-predisposing syndrome Pathogenic:5

Jun 17, 2020

Spanish ATM Cancer Susceptibility Variant Interpretation Working Group

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1564_1565del p.(Glu522Ilefs*43) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein, due to nonsense mediated decay (NMD) (PVS1). It has an allele frequency of 0.00004232 (0.004%, 10/236,314 alleles) in the gnomAD v2.1.1 non-cancer dataset, with a maximal frequency of 0.000078 (0.008%, 8/102,512 alleles) in the Non-Finnish European subpopulation (no population frequency criterion met; http://gnomad.broadinstitute.org). This variant has been reported in at least four ataxia-telangiectasia probands in trans with pathogenic variants (PMID: 15880721, 16266405) and in three homozygous probands (PMID: 12497634), which awards it with 4 points as per ClinGen SVI Recommendation for in trans Criterion (PM3_VeryStrong). It has also been observed in at least 10 other ataxia-telangiectasia probands (PMID: 9463314, 21965147, 30772474). In summary, this variant meets criteria to be classified as pathogenic. Adapted ACMG/AMP rules applied as defined by the Spanish ATM working group: PVS1 + PM3_VeryStrong (PMID: 33280026). -

Jan 08, 2024

Color Diagnostics, LLC DBA Color Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant deletes 2 nucleotides in exon 10 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast cancer (PMID: 16652348, 17393301, 29785153), pancreatic cancer (PMID: 29945567, 30067863), and gastric cancer (PMID: 31514334). This variant has also been reported in the homozygous state and in the compound heterozygous state with an additional ATM pathogenic variant in individuals affected with ataxia-telangiectasia (PMID: 10817650, 22213089, 30772474). This variant has been identified in 14/250850 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -

Sep 10, 2021

Sema4, Sema4

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Oct 23, 2024

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1564_1565delGA pathogenic mutation, located in coding exon 9 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 1564 to 1565, causing a translational frameshift with a predicted alternate stop codon (p.E522Ifs*43). This alteration is a commonly recurring mutation in Ataxia-Telangiectasia cohorts and has been observed in both the homozygous and compound heterozygous states (Byrd PJ et al. Hum. Mol. Genet. 1996 Jan;5:145-9; McConville CM et al. Am. J. Hum. Genet. 1996 Aug;59:320-30; Broeks A et al. Hum. Mutat. 1998;12:330-7; Stankovic T et al. Am. J. Hum. Genet. 1998 Feb;62:334-45; Sandoval N et al. Hum. Mol. Genet. 1999 Jan;8:69-79; Teraoka SN et al. Am. J. Hum. Genet. 1999 Jun;64:1617-31; Li A and Swift M. Am. J. Med. Genet. 2000 May;92:170-7; Verhagen MM et al. Neuropediatrics. 2007 Jun;38:117-21; Verhagen MM et al. Neurology. 2009 Aug;73:430-7; Reiman A et al. Br. J. Cancer. 2011 Aug;105:586-91; Demuth I et al. Neurogenetics. 2011 Nov;12:273-82; Verhagen MM et al. Hum. Mutat. 2012 Mar;33:561-71; van Os NJH et al. Clin. Immunol. 2017 05;178:45-55). This mutation has also been observed in patients with breast cancer (Hansford S et al. JAMA Oncol. 2015 Apr;1:23-32; Seifert BA et al. Clin. Cancer Res. 2016 Aug;22:4087-4094; Decker B et al. J. Med. Genet. 2017 Nov;54:732-741; Hauke J et al. Cancer Med. 2018 Apr;7:1349-1358). Additionally, this mutation has been identified in multiple cohorts of patients with pancreatic cancer (Shindo K et al. J. Clin. Oncol. 2017 Oct;35:3382-3390; Young EL et al. BMC Cancer. 2018 Jun;18:697; Dudley B et al. Cancer. 2018 Apr;124:1691-1700; Brand R et al. Cancer. 2018 Aug;[Epub ahead of print]). Of note, this alteration is also designated as 1560CAG>C, 1561delAG, 1561_1562delAG, 1563delAG, and 1563_1564delAG in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -

Jan 01, 2020

GeneKor MSA

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variation is a deletion of 2 nucleotides in exon 10 of the ATM mRNA (c.1564_1565delGA), causing a frameshift after codon 522 and the creation of a premature translational stop signal 43 amino acid residues later -p.(Glu522Ilefs*43). This is expected to result in an absent or disrupted protein product. Truncating variants in ATM are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with ataxia-telangiectasia and in breast cancer patients (PMID: 10817650, PMID: 12497634, PMID: 27083775). The mutation database ClinVar contains multiple entries for this variant (Variation ID: 127340). -

Breast and/or ovarian cancer Pathogenic:1

Sep 28, 2022

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

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ataxia-telangiectasia syndrome;C0346153:Familial cancer of breast Pathogenic:1

Mar 07, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ATM-related disorder Pathogenic:1

Jan 22, 2024

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The ATM c.1564_1565delGA variant is predicted to result in a frameshift and premature protein termination (p.Glu522Ilefs*43). This variant has previously been reported in patients with ataxia telangiectasia (Byrd et al. 1996. PubMed ID: 8789452), as well as in individuals with a personal or family history of breast, pancreatic, gastric, and colorectal cancers (Decker et al. 2017. PubMed ID: 28779002; Hansford et al. 2015. PubMed ID: 26182300; Huang et al. 2015. PubMed ID: 26506520; Shindo et al. 2017. PubMed ID: 28767289; Tung et al. 2014. PubMed ID: 25186627; Yurgelun et al. 2015. PubMed ID: 25980754). This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/127340/). Frameshift variants in ATM are expected to be pathogenic. This variant is interpreted as pathogenic. -

Tip-toe gait Pathogenic:1

Mar 15, 2022

Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gait disorder -

Malignant tumor of breast Pathogenic:1

-

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The ATM p.Glu522Ilefs*43 variant was identified in 24 of 22060 proband chromosomes (frequency: 0.002) from individuals or families with Ataxia-Telangiectasia, breast cancer, melanoma, or pancreatic cancer (Campbell 2003, Demuth 2011, Li 2000, Seifert 2016, Stankovic 1998, Susswein 2015, Teraoka 1999, Verhagen 2011, Mitu 2005). The variant was also identified in dbSNP (ID: rs587779817; Alias rs751357509) as "With Pathogenic allele", ClinVar (classified as pathogenic by GeneDx, Ambry Genetics, Invitae, Counsyl, Color Genomics and Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics), Cosmic (2x found in Haematopoietic and lymphoid tissue or Upper aerodigestive tract), and LOVD 3.0 (40x as pathogenic). The variant was not identified in the COGR database. The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.1564_1565del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 522 and leads to a premature stop codon at position 564. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the ATM gene are an established mechanism of disease in ATM-associated cancers and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. -

Ataxia-telangiectasia syndrome;C0027672:Hereditary cancer-predisposing syndrome Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant classified as Pathogenic and reported on 12-28-2021 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs587779817; hg19: chr11-108121752;