11-94471764-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005591.4(MRE11):​c.660-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MRE11
NM_005591.4 splice_region, intron

Scores

2
Splicing: ADA: 0.003052
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0330

Publications

0 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

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 11-94471764-A-G is Benign according to our data. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-94471764-A-G is described in CliVar as Likely_benign. Clinvar id is 1681611.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRE11NM_005591.4 linkc.660-5T>C splice_region_variant, intron_variant Intron 7 of 19 ENST00000323929.8 NP_005582.1 P49959-1A0A024R395

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRE11ENST00000323929.8 linkc.660-5T>C splice_region_variant, intron_variant Intron 7 of 19 1 NM_005591.4 ENSP00000325863.4 P49959-1
MRE11ENST00000323977.7 linkc.660-5T>C splice_region_variant, intron_variant Intron 7 of 18 1 ENSP00000326094.3 P49959-2
MRE11ENST00000407439.7 linkc.669-5T>C splice_region_variant, intron_variant Intron 7 of 19 2 ENSP00000385614.3 P49959-3
MRE11ENST00000393241.8 linkc.660-5T>C splice_region_variant, intron_variant Intron 7 of 19 5 ENSP00000376933.4 F8W7U8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Ataxia-telangiectasia-like disorder Benign:1
Feb 23, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
8.0
DANN
Benign
0.77
PhyloP100
-0.033
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0031
dbscSNV1_RF
Benign
0.12
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs587781873; hg19: chr11-94204930; API