rs376350227
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_016938.5(EFEMP2):c.348C>T(p.Asp116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
EFEMP2
NM_016938.5 synonymous
NM_016938.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.718
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 11-65871176-G-A is Benign according to our data. Variant chr11-65871176-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 472822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.718 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFEMP2 | NM_016938.5 | c.348C>T | p.Asp116= | synonymous_variant | 4/11 | ENST00000307998.11 | |
EFEMP2 | NR_037718.2 | n.473C>T | non_coding_transcript_exon_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFEMP2 | ENST00000307998.11 | c.348C>T | p.Asp116= | synonymous_variant | 4/11 | 1 | NM_016938.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251198Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135824
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461842Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727230
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74368
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 30, 2023 | - - |
Cutis laxa, autosomal recessive, type 1B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at