11-108280980-TA-TAAA

Variant names:

• chr11-108280980-T-TAA
• rs3218681
• NM_000051.4:c.3403-14_3403-13dupAA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000051.4(ATM):​c.3403-14_3403-13dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). The gene ATM is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.133
• Publications: 16 publications found

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: Ambry Genetics
• ataxia telangiectasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Laboratory for Molecular Medicine
• 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

ACMG classification

Specifications for ATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 11-108280980-T-TAA is Benign according to our data. Variant chr11-108280980-T-TAA is described in ClinVar as Likely_benign. ClinVar VariationId is 673500.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.3403-14_3403-13dupAA		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3403-14_3403-13dupAA		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.3403-15_3403-14insAA		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.3403-15_3403-14insAA		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000531525.3	TSL:1	c.3403-15_3403-14insAA		intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1409298 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 702278

African (AFR) AF: 0.00 AC: 0 AN: 31692

American (AMR) AF: 0.00 AC: 0 AN: 41766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 39270

South Asian (SAS) AF: 0.00 AC: 0 AN: 81442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074274

Other (OTH) AF: 0.00 AC: 0 AN: 58348

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs3218681; hg19: chr11-108151707;