5-149977662-GAAAGT-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000112.4(SLC26A2):c.15_19delTAAAG(p.Ser5ArgfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,570 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000112.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC26A2 | ENST00000286298.5 | c.15_19delTAAAG | p.Ser5ArgfsTer4 | frameshift_variant | Exon 2 of 3 | 1 | NM_000112.4 | ENSP00000286298.4 | ||
SLC26A2 | ENST00000433184.1 | c.15_19delTAAAG | p.Ser5ArgfsTer4 | frameshift_variant | Exon 3 of 3 | 4 | ENSP00000405496.1 | |||
SLC26A2 | ENST00000690410.1 | n.247_251delTAAAG | non_coding_transcript_exon_variant | Exon 2 of 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250066Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135346
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460570Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726722
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Diastrophic dysplasia;C0265274:Achondrogenesis, type IB;C1847593:Multiple epiphyseal dysplasia type 4;C1850554:Atelosteogenesis type II Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SLC26A2 are known to be pathogenic (PMID: 7923357, 8528239, 8571951, 10482955, 11241838, 21077202). This variant has not been reported in the literature in individuals with SLC26A2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser5Argfs*4) in the SLC26A2 gene. It is expected to result in an absent or disrupted protein product. -
Diastrophic dysplasia Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at