11-108271228-CTTTTT-CTTTT

Position:

• chr11-108271228-CTTTTT-CTTTT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.137

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 11-108271228-CT-C is Benign according to our data. Variant chr11-108271228-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 490504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108271228-CT-C is described in Lovd as [Benign]. Variant chr11-108271228-CT-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00559 (794/142066) while in subpopulation AFR AF= 0.00677 (264/38982). AF 95% confidence interval is 0.0061. There are 0 homozygotes in gnomad4. There are 445 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4	c.2922-8delT		splice_region_variant, intron_variant		ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.2922-8delT		splice_region_variant, intron_variant			NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.00554 AC: 787 AN: 142030 Hom.: 0 Cov.: 31

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

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.376 AC: 365161 AN: 971484 Hom.: 1 Cov.: 0 AF XY: 0.382 AC XY: 186052 AN XY: 486914

Gnomad4 AFR exome AF: 0.337

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.418

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.379

GnomAD4 genome AF: 0.00559 AC: 794 AN: 142066 Hom.: 0 Cov.: 31 AF XY: 0.00646 AC XY: 445 AN XY: 68924

Gnomad4 AFR AF: 0.00677

Gnomad4 AMR AF: 0.00273

Gnomad4 ASJ AF: 0.00243

Gnomad4 EAS AF: 0.00387

Gnomad4 SAS AF: 0.000226

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.00419

Gnomad4 OTH AF: 0.00359

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
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 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 2019	- -

Ataxia-telangiectasia syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Breast and/or ovarian cancer Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Jul 07, 2021

- -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Sep 19, 2016

- -

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: rs373881770; hg19: chr11-108141955;