rs746559651
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001349884.2(DRAM2):c.140del(p.Gly47ValfsTer3) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000373 in 1,607,270 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
DRAM2
NM_001349884.2 frameshift
NM_001349884.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.52
Genes affected
DRAM2 (HGNC:28769): (DNA damage regulated autophagy modulator 2) The protein encoded by this gene binds microtubule-associated protein 1 light chain 3 and is required for autophagy. Defects in this gene are a cause of retinal dystrophy. In addition, two microRNAs (microRNA 125b-1 and microRNA 144) can bind to the mRNA of this gene and produce the disease state. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-111126285-AC-A is Pathogenic according to our data. Variant chr1-111126285-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 192233.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-111126285-AC-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DRAM2 | NM_001349884.2 | c.140del | p.Gly47ValfsTer3 | frameshift_variant | 5/10 | ENST00000484310.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DRAM2 | ENST00000484310.6 | c.140del | p.Gly47ValfsTer3 | frameshift_variant | 5/10 | 1 | NM_001349884.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000664 AC: 1AN: 150714Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250778Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135552
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GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456556Hom.: 0 Cov.: 28 AF XY: 0.00000552 AC XY: 4AN XY: 724892
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cone-rod dystrophy 21 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 12, 2015 | - - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | reference population | Leeds Vision Research Group, University of Leeds | Nov 01, 2014 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at