GeneBe

NM_000051.4:c.1810_1811delCCinsAG

Variant names:
GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.
+2 Uncertain · Warm
-7
-6
-1
0
+5
+6
+9
+10
B
LB
VUS
LP
P
 The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_000051.4(ATM):c.1810_1811delCCinsAG (p.Pro604Ser) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.P604L: Uncertain_significance (ClinVar VariationId 580035, 1 star); p.P604= (synonymous): Likely_benign (ClinVar VariationId 3649564, 1 star); p.P604R: Uncertain_significance (ClinVar VariationId 2061819, 1 star); p.P604S: Benign (ClinVar VariationId 127343, 3 stars) This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

Frequency

Genomes: not found (cov: 32)

Consequence

ATM
NM_000051.4 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.22

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):
  • ATM-related cancer predisposition
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • hereditary breast carcinoma
    Inheritance: AD Classification: DEFINITIVE Submitted by: Natera, Ambry Genetics
  • ataxia telangiectasia
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen, G2P, Orphanet, Natera, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • prostate cancer
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • sarcoma
    Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
  • gastric carcinoma
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • hereditary nonpolyposis colon cancer
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000051.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

PM2Absent/extremely low in population databases
Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (threshold 0.0001) — PM2 moderate.

Variant Effect in Transcripts

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

RefSeq Transcripts

ATM NM_000051.4
MANE Select
HGVSc / HGVSpc.1810_1811delCCinsAGp.Pro604Ser
Exon rankN/A
missense
Prot: NP_000042.3
ATM NM_001351834.2
HGVSc / HGVSpc.1810_1811delCCinsAGp.Pro604Ser
Exon rankN/A
missense
Prot: NP_001338763.1UniProt: Q13315

Ensembl Transcripts

ATM ENST00000675843.1
MANE Select
HGVSc / HGVSpc.1810_1811delCCinsAGp.Pro604Ser
Exon rankN/A
missense
Prot: ENSP00000501606.1UniProt: Q13315
ATM ENST00000452508.7
TSL:1
HGVSc / HGVSpc.1810_1811delCCinsAGp.Pro604Ser
Exon rankN/A
missense
Prot: ENSP00000388058.2UniProt: Q13315
ATM ENST00000531525.3
TSL:1
HGVSc / HGVSpc.1810_1811delCCinsAGp.Pro604Ser
Exon rankN/A
missense
Prot: ENSP00000434327.3UniProt: H0YDU7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)
Rare (AF ≤ 0.0001 / Hom ≤ 1)
Global population databases 2 sources
GnomAD3 genomes
Cov:32
GnomAD4 genome
Cov:32
Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

PhyloP100
Uncertain6.2
Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

Other links and lift over

hg19: chr11-108123551;
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