rs2155209

chr11-94417624-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.631

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MRE11	NM_005591.4	c.*2501A>G		3_prime_UTR_variant	20/20	ENST00000323929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRE11	ENST00000323929.8	c.*2501A>G		3_prime_UTR_variant	20/20	1	NM_005591.4	P3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41579 AN: 152044 Hom.: 6382 Cov.: 32

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.: 0 AF XY: 0.315 AC XY: 11687 AN XY: 37084

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.358

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.273 AC: 41612 AN: 152164 Hom.: 6387 Cov.: 32 AF XY: 0.273 AC XY: 20266 AN XY: 74368

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.286

Alfa AF: 0.319 Hom.: 10096

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

Submissions by phenotype

Ataxia-telangiectasia-like disorder 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

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
Dann	Benign	0.65
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

LitVar

Other links and lift over

dbSNP: rs2155209; hg19: chr11-94150790;