11-108271228-CTT-C

Position:

• chr11-108271228-CTT-C

Variant summary

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

The NM_000051.4(ATM):​c.2922-9_2922-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,485,054 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 0.00029 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0054 (0 hom.)
• Consequence: ATM NM_000051.4 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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-CTT-C is Benign according to our data. Variant chr11-108271228-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1802800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108271228-CTT-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00545 (7314/1342764) while in subpopulation AMR AF= 0.00925 (388/41936). AF 95% confidence interval is 0.00849. There are 0 homozygotes in gnomad4_exome. There are 3656 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4	c.2922-9_2922-8delTT		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.2922-9_2922-8delTT		splice_region_variant, intron_variant			NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.000288 AC: 41 AN: 142240 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000771

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00256

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000201

Gnomad OTH AF: 0.000515

GnomAD4 exome AF: 0.00545 AC: 7314 AN: 1342764 Hom.: 0 AF XY: 0.00546 AC XY: 3656 AN XY: 670018

Gnomad4 AFR exome AF: 0.00688

Gnomad4 AMR exome AF: 0.00925

Gnomad4 ASJ exome AF: 0.00764

Gnomad4 EAS exome AF: 0.00631

Gnomad4 SAS exome AF: 0.00709

Gnomad4 FIN exome AF: 0.0115

Gnomad4 NFE exome AF: 0.00470

Gnomad4 OTH exome AF: 0.00615

GnomAD4 genome AF: 0.000288 AC: 41 AN: 142290 Hom.: 0 Cov.: 31 AF XY: 0.000275 AC XY: 19 AN XY: 69080

Gnomad4 AFR AF: 0.0000769

Gnomad4 AMR AF: 0.000140

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00256

Gnomad4 NFE AF: 0.000201

Gnomad4 OTH AF: 0.000511

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

Breast and/or ovarian cancer Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Jun 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;