3-146070724-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_182943.3(PLOD2):c.2270A>T(p.Asp757Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_182943.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLOD2 | NM_182943.3 | c.2270A>T | p.Asp757Val | missense_variant | Exon 20 of 20 | ENST00000282903.10 | NP_891988.1 | |
PLOD2 | NM_000935.3 | c.2207A>T | p.Asp736Val | missense_variant | Exon 19 of 19 | NP_000926.2 | ||
PLOD2 | XM_017006625.3 | c.1994A>T | p.Asp665Val | missense_variant | Exon 21 of 21 | XP_016862114.1 | ||
PLOD2 | XM_047448319.1 | c.1994A>T | p.Asp665Val | missense_variant | Exon 20 of 20 | XP_047304275.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.91e-7 AC: 1AN: 1447476Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1AN XY: 720752
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Bruck syndrome 2 Uncertain:1
This PLOD2 variant is absent in a large population dataset and has not been reported previously in the literature to our knowledge. Three bioinformatic tools queried predict that p.Asp757Val would be damaging. The asparagine residue at this position is strongly conserved across all vertebrate species assessed. This variant is not predicted to affect normal exon 20 splicing, although this has not been confirmed experimentally to our knowledge. Due to insufficient evidence, we consider the clinical significance of c.2270A>T to be uncertain at this time. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at