rs777036353
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong
The NM_000051.4(ATM):c.6199-18_6199-15del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,302 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 28)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
ATM
NM_000051.4 splice_polypyrimidine_tract, intron
NM_000051.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.87
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]
C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 11-108317354-CAAAA-C is Benign according to our data. Variant chr11-108317354-CAAAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 490642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.6199-18_6199-15del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.6199-18_6199-15del | splice_polypyrimidine_tract_variant, intron_variant | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250858Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135688
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GnomAD4 exome AF: 0.00000275 AC: 4AN: 1454302Hom.: 0 AF XY: 0.00000414 AC XY: 3AN XY: 723780
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GnomAD4 genome ? Cov.: 28
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Familial cancer of breast Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Jun 03, 2024 | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 30, 2015 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at