chr11-65866752-G-GC
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016938.5(EFEMP2):c.*165_*166insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000461 in 889,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
EFEMP2
NM_016938.5 3_prime_UTR
NM_016938.5 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.118
Genes affected
EFEMP2 (HGNC:3219): (EGF containing fibulin extracellular matrix protein 2) A large number of extracellular matrix proteins have been found to contain variations of the epidermal growth factor (EGF) domain and have been implicated in functions as diverse as blood coagulation, activation of complement and determination of cell fate during development. The protein encoded by this gene contains four EGF2 domains and six calcium-binding EGF2 domains. This gene is necessary for elastic fiber formation and connective tissue development. Defects in this gene are cause of an autosomal recessive cutis laxa syndrome. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]
MUS81 (HGNC:29814): (MUS81 structure-specific endonuclease subunit) This gene encodes a structure-specific endonuclease which belongs to the XPF/MUS81 endonuclease family and plays a critical role in the resolution of recombination intermediates during DNA repair after inter-strand cross-links, replication fork collapse, and DNA double-strand breaks. The encoded protein associates with one of two closely related essential meiotic endonuclease proteins (EME1 or EME2) to form a complex that processes DNA secondary structures. It contains an N-terminal DEAH helicase domain, an excision repair cross complementation group 4 (ERCC4) endonuclease domain, and two tandem C-terminal helix-hairpin-helix domains. Mice with a homozygous knockout of the orthologous gene have significant meiotic defects including the failure to repair a subset of DNA double strand breaks. [provided by RefSeq, Jun 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFEMP2 | NM_016938.5 | c.*165_*166insG | 3_prime_UTR_variant | 11/11 | ENST00000307998.11 | ||
EFEMP2 | NR_037718.2 | n.1531-41_1531-40insG | intron_variant, non_coding_transcript_variant | ||||
MUS81 | NR_146598.2 | n.1813-498dup | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFEMP2 | ENST00000307998.11 | c.*165_*166insG | 3_prime_UTR_variant | 11/11 | 1 | NM_016938.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152072Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000855 AC: 12AN: 140366Hom.: 0 AF XY: 0.0000132 AC XY: 1AN XY: 75840
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GnomAD4 exome AF: 0.0000515 AC: 38AN: 737348Hom.: 0 Cov.: 9 AF XY: 0.0000362 AC XY: 14AN XY: 386452
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cutis laxa, recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at