1-111118224-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_001349884.2(DRAM2):āc.737T>Cā(p.Leu246Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000561 in 1,612,948 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001349884.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DRAM2 | NM_001349884.2 | c.737T>C | p.Leu246Pro | missense_variant | Exon 10 of 10 | ENST00000484310.6 | NP_001336813.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 151998Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000335 AC: 84AN: 250858Hom.: 0 AF XY: 0.000332 AC XY: 45AN XY: 135584
GnomAD4 exome AF: 0.000587 AC: 858AN: 1460950Hom.: 1 Cov.: 30 AF XY: 0.000566 AC XY: 411AN XY: 726764
GnomAD4 genome AF: 0.000309 AC: 47AN: 151998Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74268
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:3
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This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 246 of the DRAM2 protein (p.Leu246Pro). This variant is present in population databases (rs148031211, gnomAD 0.07%). This missense change has been observed in individual(s) with inherited retinal disease (PMID: 32483926, 35806404; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 863836). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. -
Cone-rod dystrophy 21 Uncertain:1
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Retinal dystrophy Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at