rs2155209

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005591.4(MRE11):c.*2501A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 232,864 control chromosomes in the GnomAD database, including 10,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6387 hom., cov: 32)

Exomes 𝑓: 0.31 ( 4025 hom. )

Consequence

MRE11
NM_005591.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.631

Publications

28 publications found

Variant links:

Genes affected

MRE11 (HGNC:7230): (MRE11 homolog, double strand break repair nuclease) This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MRE11 Gene-Disease associations (from GenCC):

ataxia-telangiectasia-like disorder 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
prostate cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

MRE11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-94417624-T-C is Benign according to our data. Variant chr11-94417624-T-C is described in ClinVar as [Benign]. Clinvar id is 306450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4 link	c.*2501A>G		3_prime_UTR_variant	Exon 20 of 20	ENST00000323929.8	NP_005582.1	P49959-1A0A024R395

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8 link	c.*2501A>G		3_prime_UTR_variant	Exon 20 of 20	1	NM_005591.4	ENSP00000325863.4		P49959-1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41579

AN:

152044

Hom.:

6382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.278

GnomAD4 exome

AF:

0.313

AC:

25237

AN:

80700

Hom.:

4025

Cov.:

AF XY:

0.315

AC XY:

11687

AN XY:

37084

show subpopulations

African (AFR)

AF:

0.130

AC:

506

AN:

3892

American (AMR)

AF:

0.317

AC:

791

AN:

2496

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

1831

AN:

5112

East Asian (EAS)

AF:

0.260

AC:

2949

AN:

11340

South Asian (SAS)

AF:

0.225

AC:

157

AN:

698

European-Finnish (FIN)

AF:

0.224

AC:

AN:

Middle Eastern (MID)

AF:

0.313

AC:

154

AN:

492

European-Non Finnish (NFE)

AF:

0.337

AC:

16804

AN:

49858

Other (OTH)

AF:

0.301

AC:

2032

AN:

6754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

907

1815

2722

3630

4537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.273

AC:

41612

AN:

152164

Hom.:

6387

Cov.:

AF XY:

0.273

AC XY:

20266

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.131

AC:

5428

AN:

41530

American (AMR)

AF:

0.301

AC:

4592

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1324

AN:

3468

East Asian (EAS)

AF:

0.275

AC:

1425

AN:

5174

South Asian (SAS)

AF:

0.226

AC:

1089

AN:

4818

European-Finnish (FIN)

AF:

0.328

AC:

3470

AN:

10582

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23055

AN:

67996

Other (OTH)

AF:

0.286

AC:

603

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1492

2984

4475

5967

7459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.313

Hom.:

11948

Bravo

AF:

0.268

Asia WGS

AF:

0.259

AC:

902

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ataxia-telangiectasia-like disorder 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Oct 29, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26735576) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.63

(source)

DANN

Benign

0.65

PhyloP100

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Publications

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rs2155209

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over