chr5-69419644-A-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001038603.3(MARVELD2):c.259A>T(p.Lys87Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,882 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001038603.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARVELD2 | NM_001038603.3 | c.259A>T | p.Lys87Ter | stop_gained | 2/7 | ENST00000325631.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARVELD2 | ENST00000325631.10 | c.259A>T | p.Lys87Ter | stop_gained | 2/7 | 1 | NM_001038603.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250798Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135724
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461882Hom.: 0 Cov.: 35 AF XY: 0.0000193 AC XY: 14AN XY: 727244
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 27, 2023 | This variant is present in population databases (rs776953681, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Lys87*) in the MARVELD2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MARVELD2 are known to be pathogenic (PMID: 17186462). This variant has not been reported in the literature in individuals affected with MARVELD2-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1446607). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at