NM_000051.4:c.2466+910G>A

Variant names:

• chr11-108259985-G-A
• rs11212570
• NM_000051.4:c.2466+910G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000051.4(ATM):​c.2466+910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 149,010 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.074 (536 hom., cov: 32)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 19 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):

• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

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	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.2466+910G>A		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.2466+910G>A		intron	N/A	NP_001338763.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.2466+910G>A		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.2466+910G>A		intron	N/A	ENSP00000388058.2
	ATM	ENST00000531525.3	TSL:1	c.2466+910G>A		intron	N/A	ENSP00000434327.3

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11044 AN: 148980 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0359

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0323

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0741 AC: 11044 AN: 149010 Hom.: 536 Cov.: 32 AF XY: 0.0715 AC XY: 5181 AN XY: 72496

African (AFR) AF: 0.0210 AC: 853 AN: 40604

American (AMR) AF: 0.0750 AC: 1119 AN: 14926

Ashkenazi Jewish (ASJ) AF: 0.0359 AC: 124 AN: 3452

East Asian (EAS) AF: 0.149 AC: 764 AN: 5116

South Asian (SAS) AF: 0.0171 AC: 81 AN: 4744

European-Finnish (FIN) AF: 0.0680 AC: 631 AN: 9276

Middle Eastern (MID) AF: 0.0315 AC: 9 AN: 286

European-Non Finnish (NFE) AF: 0.107 AC: 7247 AN: 67650

Other (OTH) AF: 0.0714 AC: 146 AN: 2044

Alfa AF: 0.0934 Hom.: 1516

Bravo AF: 0.0723

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.020
DANN	Benign	0.19
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11212570; hg19: chr11-108130712; COSMIC: COSV53777925;