rs61893867
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_016938.5(EFEMP2):c.1226G>A(p.Arg409Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R409W) has been classified as Uncertain significance.
Frequency
Consequence
NM_016938.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFEMP2 | NM_016938.5 | c.1226G>A | p.Arg409Gln | missense_variant | 11/11 | ENST00000307998.11 | |
EFEMP2 | NR_037718.2 | n.1351G>A | non_coding_transcript_exon_variant | 11/12 | |||
MUS81 | NR_146598.2 | n.1813-233C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFEMP2 | ENST00000307998.11 | c.1226G>A | p.Arg409Gln | missense_variant | 11/11 | 1 | NM_016938.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251214Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135874
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 727230
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
ClinVar
Submissions by phenotype
Cutis laxa, autosomal recessive, type 1B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 16, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 409 of the EFEMP2 protein (p.Arg409Gln). This variant is present in population databases (rs61893867, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with EFEMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 39010). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cutis laxa, autosomal recessive, type 1A Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at