rs2155209

Variant names:

• chr11-94417624-T-C
• rs2155209
• NM_005591.4:c.*2501A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 publications found

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: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005591.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRE11	NM_005591.4	MANE Select	c.*2501A>G		3_prime_UTR	Exon 20 of 20	NP_005582.1	P49959-1
	MRE11	NM_001440460.1		c.*2501A>G		3_prime_UTR	Exon 21 of 21	NP_001427389.1
	MRE11	NM_001440461.1		c.*2501A>G		3_prime_UTR	Exon 21 of 21	NP_001427390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRE11	ENST00000323929.8	TSL:1 MANE Select	c.*2501A>G		3_prime_UTR	Exon 20 of 20	ENSP00000325863.4	P49959-1
	MRE11	ENST00000856310.1		c.*2501A>G		3_prime_UTR	Exon 20 of 20	ENSP00000526369.1
	MRE11	ENST00000856311.1		c.*2501A>G		3_prime_UTR	Exon 20 of 20	ENSP00000526370.1

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

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: 13 AN: 58

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

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

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: 81 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23055 AN: 67996

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.313 Hom.: 11948

Bravo AF: 0.268

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ataxia-telangiectasia-like disorder 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
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

Other links and lift over

dbSNP: rs2155209; hg19: chr11-94150790;