rs794726688
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_019032.6(ADAMTSL4):c.826_836delCGTGCATCCCC(p.Arg276SerfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,868 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R276R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_019032.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000724 AC: 11AN: 152022Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000155 AC: 39AN: 251250Hom.: 1 AF XY: 0.0000810 AC XY: 11AN XY: 135832
GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461846Hom.: 1 AF XY: 0.0000454 AC XY: 33AN XY: 727224
GnomAD4 genome AF: 0.0000724 AC: 11AN: 152022Hom.: 0 Cov.: 30 AF XY: 0.0000673 AC XY: 5AN XY: 74270
ClinVar
Submissions by phenotype
Ectopia lentis 2, isolated, autosomal recessive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2010 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 30, 2024 | This sequence change creates a premature translational stop signal (p.Arg276Serfs*21) in the ADAMTSL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADAMTSL4 are known to be pathogenic (PMID: 20564469, 28642162). This variant is present in population databases (rs754883702, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with ectopia lentis (PMID: 20564469). ClinVar contains an entry for this variant (Variation ID: 39556). For these reasons, this variant has been classified as Pathogenic. - |
Ectopia lentis et pupillae Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2010 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at