VCV000136470.23 - ClinVar

NM_001184.4(ATR):c.7274G>A (p.Arg2425Gln)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign

11 out of 11 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001184.4(ATR):c.7274G>A (p.Arg2425Gln)

Variation ID: 136470 Accession: VCV000136470.23

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q23 3: 142459302 (GRCh38) [ NCBI UCSC ] 3: 142178144 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 23, 2014	Aug 30, 2025	Jul 10, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001184.4:c.7274G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001175.2:p.Arg2425Gln	missense
NM_001354579.2:c.7082G>A	NP_001341508.1:p.Arg2361Gln	missense
NC_000003.12:g.142459302C>T
NC_000003.11:g.142178144C>T
NG_008951.1:g.124525G>A
LRG_1403:g.124525G>A
LRG_1403t1:c.7274G>A	LRG_1403p1:p.Arg2425Gln
	Q13535:p.Arg2425Gln

... more HGVS ... less HGVS

Protein change

R2425Q, R2361Q

Other names

p.R2425Q:CGA>CAA

Canonical SPDI

NC_000003.12:142459301:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.10224 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.09963

Exome Aggregation Consortium (ExAC) 0.13279

The Genome Aggregation Database (gnomAD) 0.12724

The Genome Aggregation Database (gnomAD), exomes 0.13060

The Genome Aggregation Database (gnomAD) 0.12815

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.13417

1000 Genomes Project 0.10224

Trans-Omics for Precision Medicine (TOPMed) 0.12036

Links

ClinGen: CA171378 UniProtKB: Q13535#VAR_041598 dbSNP: rs2229032 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ATR		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	4067	4190

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (3)	criteria provided, multiple submitters, no conflicts	Mar 28, 2016	RCV000145330.10
Seckel syndrome 1	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 8, 2023	RCV000321936.7
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Feb 4, 2025	RCV000586392.10
Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 7, 2023	RCV003126504.2
Hereditary cancer-predisposing syndrome	Benign (1)	criteria provided, single submitter	Jul 10, 2025	RCV005629493.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Aug 15, 2013) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2007)	not specified (Autosomal recessive inheritance)	Genetic Services Laboratory, University of Chicago Accession: SCV000192408.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jul 07, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004015590.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Jul 10, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary cancer-predisposing syndrome	GeneKor MSA Accession: SCV006311422.1 First in ClinVar: Aug 30, 2025 Last updated: Aug 30, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Mar 28, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000538377.1 First in ClinVar: May 29, 2016 Last updated: May 29, 2016	Comment: show Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Method: Genome/Exome Filtration

Benign (Apr 27, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not provided	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000697787.1 First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018	Publications: PubMed (1) PubMed: 17010193 Comment: show Variant summary: The c.7274G>A variant involves the alteration of a non-conserved nucleotide and 4/4 in silico tools predict a neutral outcome. The variant was observed in the large, broad control population, ExAC, with an allele frequency of 13.3% which includes 1212 homozygous occurrences, strong evidence this variant is a benign polymorphism. The variant has been reported as benign by multiple reputable clinical labs/publications. Taken together, this variant has been classified as Benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Dec 18, 2013) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000167130.10 First in ClinVar: Jun 23, 2014 Last updated: May 29, 2016	Comment: show This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Seckel syndrome 1	Illumina Laboratory Services, Illumina Accession: SCV000441395.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Feb 08, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Seckel syndrome 1	Genome-Nilou Lab Accession: SCV003802575.1 First in ClinVar: Feb 18, 2023 Last updated: Feb 18, 2023	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Feb 08, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome	Genome-Nilou Lab Accession: SCV003802576.1 First in ClinVar: Feb 18, 2023 Last updated: Feb 18, 2023	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005302980.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Feb 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001729233.5 First in ClinVar: Jun 15, 2021 Last updated: Feb 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Comment:

Variant summary: The c.7274G>A variant involves the alteration of a non-conserved nucleotide and 4/4 in silico tools predict a neutral outcome. The variant was observed in the large, broad control population, ExAC, with an allele frequency of 13.3% which includes 1212 homozygous occurrences, strong evidence this variant is a benign polymorphism. The variant has been reported as benign by multiple reputable clinical labs/publications. Taken together, this variant has been classified as Benign.

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families.	Durocher F	BMC cancer	2006	PMID: 17010193

Text-mined citations for rs2229032 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 07, 2025