GeneBe

NM_000051.4:c.2125-7_2125-3delCTTTA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP6

The NM_000051.4(ATM):​c.2125-7_2125-3delCTTTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,344 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ATM
NM_000051.4 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.63

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • hereditary breast carcinoma
    Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
  • ataxia telangiectasia
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Orphanet
  • hereditary nonpolyposis colon cancer
    Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
  • prostate cancer
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • sarcoma
    Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
  • familial ovarian cancer
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • gastric carcinoma
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 11-108256203-GTTTAC-G is Benign according to our data. Variant chr11-108256203-GTTTAC-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 414542.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ATM
NM_000051.4
MANE Select
c.2125-7_2125-3delCTTTA
splice_region intron
N/ANP_000042.3
ATM
NM_001351834.2
c.2125-7_2125-3delCTTTA
splice_region intron
N/ANP_001338763.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ATM
ENST00000675843.1
MANE Select
c.2125-11_2125-7delTTTAC
splice_region intron
N/AENSP00000501606.1
ATM
ENST00000452508.7
TSL:1
c.2125-11_2125-7delTTTAC
splice_region intron
N/AENSP00000388058.2
ATM
ENST00000531525.3
TSL:1
c.2125-11_2125-7delTTTAC
splice_region intron
N/AENSP00000434327.3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1436344
Hom.:
0
AF XY:
0.00000140
AC XY:
1
AN XY:
714508
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32982
American (AMR)
AF:
0.00
AC:
0
AN:
44028
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25640
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38914
South Asian (SAS)
AF:
0.0000121
AC:
1
AN:
82736
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51640
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5678
European-Non Finnish (NFE)
AF:
9.13e-7
AC:
1
AN:
1095604
Other (OTH)
AF:
0.00
AC:
0
AN:
59122
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Dec 16, 2021
Sema4, Sema4
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:curation

May 31, 2017
Color Diagnostics, LLC DBA Color Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Ataxia-telangiectasia syndrome Benign:1
Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1060504272; hg19: chr11-108126930; API