rs772719886
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000051.4(ATM):c.2124+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000702 in 1,609,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )
Consequence
ATM
NM_000051.4 intron
NM_000051.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.310
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 11-108254053-A-G is Benign according to our data. Variant chr11-108254053-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 490453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.2124+14A>G | intron_variant | ENST00000675843.1 | NP_000042.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.2124+14A>G | intron_variant | NM_000051.4 | ENSP00000501606 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247220Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134396
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GnomAD4 exome AF: 0.0000755 AC: 110AN: 1457204Hom.: 0 Cov.: 29 AF XY: 0.0000731 AC XY: 53AN XY: 725186
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The ATM c.2124+14A>G variant was not identified in the literature nor was it identified in the LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs772719886) as "With Likely benign allele", and in ClinVar (classified as likely benign by Color). The variant was identified in control databases in 4 of 242842 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 15042 chromosomes (freq: 0.00007), European in 3 of 109946 chromosomes (freq: 0.00003), while the variant was not observed in the Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Ataxia-telangiectasia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 03, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at