NM_000051.4(ATM):c.7816A>G (p.Ile2606Val) AND Familial cancer of breast

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Mar 30, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002265647.12

Allele description [Variation Report for NM_000051.4(ATM):c.7816A>G (p.Ile2606Val)]

NM_000051.4(ATM):c.7816A>G (p.Ile2606Val)

Genes:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.7816A>G (p.Ile2606Val)

HGVS:

NC_000011.10:g.108332789A>G
NG_009830.1:g.114958A>G
NG_054724.1:g.142044T>C
NM_000051.4:c.7816A>GMANE SELECT
NM_001330368.2:c.641-23718T>C
NM_001351110.2:c.*38+2431T>C
NM_001351834.2:c.7816A>G
NP_000042.3:p.Ile2606Val
NP_000042.3:p.Ile2606Val
NP_001338763.1:p.Ile2606Val
LRG_135t1:c.7816A>G
LRG_135:g.114958A>G
LRG_135p1:p.Ile2606Val
NC_000011.9:g.108203516A>G
NM_000051.3:c.7816A>G
p.I2606V

Protein change:

I2606V

Links:

dbSNP: rs376824528

NCBI 1000 Genomes Browser:

rs376824528

Molecular consequence:

NM_001330368.2:c.641-23718T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+2431T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7816A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7816A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002548546	Department of Molecular Diagnostics, Institute of Oncology Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35806449, 25741868
SCV004019654	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely benign (Mar 31, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV004207706	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002548546

Department of Molecular Diagnostics, Institute of Oncology Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 15, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004019654

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely benign
(Mar 31, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV004207706

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of Spliceogenic Variants beyond Canonical GT-AG Splice Sites in Hereditary Cancer Genes.

Dragoš VŠ, Strojnik K, Klančar G, Škerl P, Stegel V, Blatnik A, Banjac M, Krajc M, Novaković S.

Int J Mol Sci. 2022 Jul 4;23(13). doi:pii: 7446. 10.3390/ijms23137446.

PubMed [citation]

PMID:: 35806449
PMCID:: PMC9267136

Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes.

Pruss D, Morris B, Hughes E, Eggington JM, Esterling L, Robinson BS, van Kan A, Fernandes PH, Roa BB, Gutin A, Wenstrup RJ, Bowles KR.

Breast Cancer Res Treat. 2014 Aug;147(1):119-32. doi: 10.1007/s10549-014-3065-9. Epub 2014 Aug 2.

PubMed [citation]

PMID:: 25085752

See all PubMed Citations (3)

Details of each submission

From Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SCV002548546.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

ATM:c.7816A>G variant is predicted to create a de novo donor ss 28 bp upstream of natural splice site. Functional RNA study has shown that the variant may cause minimally expressed whole exon 53 skipping (PMID: 35806449). Missense in silico tools predict that the variant does not have an impact on protein function (REVEL 0.26). Therefore the variant was classified as variant of uncertain significance (ACMG/AMP: PP3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004019654.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004207706.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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