NM_000051.4(ATM):c.7174C>T (p.Arg2392Trp) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 14, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000590313.17

Allele description [Variation Report for NM_000051.4(ATM):c.7174C>T (p.Arg2392Trp)]

NM_000051.4(ATM):c.7174C>T (p.Arg2392Trp)

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.7174C>T (p.Arg2392Trp)

HGVS:

NC_000011.10:g.108329105C>T
NG_009830.1:g.111274C>T
NG_054724.1:g.145728G>A
NM_000051.4:c.7174C>TMANE SELECT
NM_001330368.2:c.641-20034G>A
NM_001351110.2:c.*38+6115G>A
NM_001351834.2:c.7174C>T
NP_000042.3:p.Arg2392Trp
NP_000042.3:p.Arg2392Trp
NP_001338763.1:p.Arg2392Trp
LRG_135t1:c.7174C>T
LRG_135:g.111274C>T
LRG_135p1:p.Arg2392Trp
NC_000011.9:g.108199832C>T
NM_000051.3:c.7174C>T
p.R2392W

Protein change:

R2392W

Links:

dbSNP: rs149827260

NCBI 1000 Genomes Browser:

rs149827260

Molecular consequence:

NM_001330368.2:c.641-20034G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+6115G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7174C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000292480	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 14, 2024)	germline	clinical testing	Citation Link,
SCV004222094	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jul 14, 2017)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 34262154, 33850299, 32832836, 32885271, 33646313, 31921681, 26787654, 23555315, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000292480

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 14, 2024)

germline

clinical testing

Citation Link,

SCV004222094

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jul 14, 2017)

unknown

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.

Dalmasso B, Pastorino L, Nathan V, Shah NN, Palmer JM, Howlie M, Johansson PA, Freedman ND, Carter BD, Beane-Freeman L, Hicks B, Molven A, Helgadottir H, Sankar A, Tsao H, Stratigos AJ, Helsing P, Van Doorn R, Gruis NA, Visser M, Wadt KAW, Mann G, et al.

Genet Med. 2021 Nov;23(11):2087-2095. doi: 10.1038/s41436-021-01240-8. Epub 2021 Jul 14.

PubMed [citation]

PMID:: 34262154
PMCID:: PMC8553617

Targeted gene panels identify a high frequency of pathogenic germline variants in patients diagnosed with a hematological malignancy and at least one other independent cancer.

Singhal D, Hahn CN, Feurstein S, Wee LYA, Moma L, Kutyna MM, Chhetri R, Eshraghi L, Schreiber AW, Feng J, Wang PP, Babic M, Parker WT, Gao S, Moore S, Das S, Thomas D, Pattnaik S, Brown AL, D'Andrea RJ, Poplawski NK, Thomas D, et al.

Leukemia. 2021 Nov;35(11):3245-3256. doi: 10.1038/s41375-021-01246-w. Epub 2021 Apr 13.

PubMed [citation]

PMID:: 33850299

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000292480.16

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Observed in individuals with a personal or family history including breast, ovarian, prostate, and other cancers (PMID: 23555315, 33646313, 31921681, 34262154, 32885271, 32832836); This variant is associated with the following publications: (PMID: 26787654, 23555315, 33646313, 31921681, 23532176, 32885271, 33850299, 32832836, 34262154)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004222094.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The frequency of this variant in the general population, 0.00072 (18/24964 chromosomes in African/African American subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. In the published literature, the variant has been reported in individuals affected with breast cancer (PMID: 33646313 (2021), 26787654 (2016), and 23555315 (2013)) and breast or ovarian cancer (PMID: 31921681 (2019)). It has also been reported in individuals with prostate cancer (PMID: 32832836 (2020)), melanoma (PMID: 34262154 (2021)), and myeloid neoplasm (PMID: 33850299 (2021)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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: Oct 13, 2024

ClinVar

Relating variation to medicine