chr2-19994297-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate
The NM_002381.5(MATN3):c.1405+2T>C variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.000107 in 1,601,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002381.5 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000525 AC: 8AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000568 AC: 14AN: 246396Hom.: 0 AF XY: 0.0000599 AC XY: 8AN XY: 133590
GnomAD4 exome AF: 0.000113 AC: 164AN: 1449540Hom.: 0 Cov.: 28 AF XY: 0.000111 AC XY: 80AN XY: 721606
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74380
ClinVar
Submissions by phenotype
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. This variant has not been reported in the literature in individuals affected with MATN3-related conditions. This variant is present in population databases (rs764727429, gnomAD 0.01%). This sequence change falls in intron 7 of the MATN3 gene. It does not directly change the encoded amino acid sequence of the MATN3 protein. It affects a nucleotide within the consensus splice site. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at