rs672655

Positions:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000051.4(ATM):c.2377-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,410,390 control chromosomes in the GnomAD database, including 217,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20115 hom., cov: 32)

Exomes 𝑓: 0.56 ( 197198 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.18

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 11-108258930-A-G is Benign according to our data. Variant chr11-108258930-A-G is described in ClinVar as [Benign]. Clinvar id is 1177614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108258930-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATM	NM_000051.4 linkuse as main transcript	c.2377-56A>G		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1 linkuse as main transcript	c.2377-56A>G		intron_variant			NM_000051.4	P1

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75137

AN:

151940

Hom.:

20105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.607

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.538

GnomAD4 exome

AF:

0.556

AC:

699635

AN:

1258332

Hom.:

197198

AF XY:

0.560

AC XY:

355690

AN XY:

635680

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.629

Gnomad4 ASJ exome

AF:

0.612

Gnomad4 EAS exome

AF:

0.430

Gnomad4 SAS exome

AF:

0.597

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.557

Gnomad4 OTH exome

AF:

0.549

GnomAD4 genome

AF:

0.494

AC:

75167

AN:

152058

Hom.:

20115

Cov.:

AF XY:

0.503

AC XY:

37388

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.607

Gnomad4 ASJ

AF:

0.640

Gnomad4 EAS

AF:

0.421

Gnomad4 SAS

AF:

0.604

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.539

Alfa

AF:

0.511

Hom.:

2984

Bravo

AF:

0.481

Asia WGS

AF:

0.531

AC:

1844

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Ataxia-telangiectasia syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over