9-133538347-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1_ModeratePM2PP3_StrongPP5
The NM_014694.4(ADAMTSL2):c.234-2A>G variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Consequence
NM_014694.4 splice_acceptor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTSL2 | NM_014694.4 | c.234-2A>G | splice_acceptor_variant | ENST00000651351.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTSL2 | ENST00000651351.2 | c.234-2A>G | splice_acceptor_variant | NM_014694.4 | P1 | ||||
ADAMTSL2 | ENST00000354484.8 | c.234-2A>G | splice_acceptor_variant | 1 | P1 | ||||
ADAMTSL2 | ENST00000393060.1 | c.234-2A>G | splice_acceptor_variant | 1 | P1 | ||||
ADAMTSL2 | ENST00000393061.7 | c.561-2A>G | splice_acceptor_variant | 1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251038Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135824
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461080Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726854
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Geleophysic dysplasia 1 Pathogenic:1
Pathogenic, no assertion criteria provided | research | Laboratory of Metabolic Disorders, Peking University First Hospital | Jun 17, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at