11-108271228-CTTTTT-CTTTTTTT

Position:

• chr11-108271228-CTTTTT-CTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000051.4(ATM):​c.2922-9_2922-8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,564,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: ATM NM_000051.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter 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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 11-108271228-C-CTT is Benign according to our data. Variant chr11-108271228-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 2692169.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000442 AC: 63 AN: 142520 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.000513

GnomAD4 exome AF: 0.000224 AC: 318 AN: 1422396 Hom.: 0 Cov.: 0 AF XY: 0.000219 AC XY: 155 AN XY: 708678

Gnomad4 AFR exome AF: 0.00147

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.0000509

Gnomad4 SAS exome AF: 0.000118

Gnomad4 FIN exome AF: 0.0000397

Gnomad4 NFE exome AF: 0.000165

Gnomad4 OTH exome AF: 0.000237

GnomAD4 genome AF: 0.000435 AC: 62 AN: 142572 Hom.: 0 Cov.: 31 AF XY: 0.000419 AC XY: 29 AN XY: 69246

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.000209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000115

Gnomad4 NFE AF: 0.000154

Gnomad4 OTH AF: 0.000509

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Feb 06, 2024

- -

ATM-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 27, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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;