chr2-71667391-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001130987.2(DYSF):c.5333C>A(p.Pro1778Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00035 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.5333C>A | p.Pro1778Gln | missense_variant | 48/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.5216C>A | p.Pro1739Gln | missense_variant | 47/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.5333C>A | p.Pro1778Gln | missense_variant | 48/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.5216C>A | p.Pro1739Gln | missense_variant | 47/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000562 AC: 141AN: 250878Hom.: 0 AF XY: 0.000604 AC XY: 82AN XY: 135742
GnomAD4 exome AF: 0.000350 AC: 511AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.000378 AC XY: 275AN XY: 727214
GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74472
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 09, 2020 | This variant is associated with the following publications: (PMID: 30564623, 27647186) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 04, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2018 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Uncertain:2Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 06, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 10, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Miyoshi muscular dystrophy 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 28, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Qualitative or quantitative defects of dysferlin Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Feb 13, 2018 | The DYSF gene is the only gene in which variants are known to cause dysferlinopathy. The DYSF c.5216C>A (p.Pro1739Gln) missense variant has been reported in one study in which it is found in two siblings from a family with a history of dysferlinopathy. The variant was found in a compound heterozygous state with a deletion in one sibling and in a heterozygous state in the other (Jin et al. 2016). Both siblings were found to be negative for dysferlin expression using immunohistochemical analysis of muscle tissue (Jin et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.005924 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the evidence, the p.Pro1739Gln variant is classified as a variant of unknown significance but suspicious for pathogenicity for dysferlinopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Distal myopathy with anterior tibial onset Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
DYSF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 06, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at