2-71669174-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP6
The NM_001130987.2(DYSF):c.5609C>T(p.Thr1870Met) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,610,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1870S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.5609C>T | p.Thr1870Met | missense_variant | 50/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.5492C>T | p.Thr1831Met | missense_variant | 49/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.5609C>T | p.Thr1870Met | missense_variant | 50/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.5492C>T | p.Thr1831Met | missense_variant | 49/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000695 AC: 17AN: 244432Hom.: 0 AF XY: 0.0000834 AC XY: 11AN XY: 131820
GnomAD4 exome AF: 0.000110 AC: 161AN: 1458214Hom.: 0 Cov.: 31 AF XY: 0.0000966 AC XY: 70AN XY: 724782
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74322
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 08, 2022 | Variant summary: DYSF c.5492C>T (p.Thr1831Met) results in a non-conservative amino acid change located in one of the C2 domains (IPR000008) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7e-05 in 244432 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in DYSF causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive (7e-05 vs 0.0031), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.5492C>T in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and both of them classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 29, 2021 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Qualitative or quantitative defects of dysferlin Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at