chr2-71660631-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_001130987.2(DYSF):c.4983G>T(p.Thr1661Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
DYSF
NM_001130987.2 synonymous
NM_001130987.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.60
Genes affected
DYSF (HGNC:3097): (dysferlin) The protein encoded by this gene belongs to the ferlin family and is a skeletal muscle protein found associated with the sarcolemma. It is involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. In addition, the protein encoded by this gene binds caveolin-3, a skeletal muscle membrane protein which is important in the formation of caveolae. Specific mutations in this gene have been shown to cause autosomal recessive limb girdle muscular dystrophy type 2B (LGMD2B) as well as Miyoshi myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 2-71660631-G-T is Benign according to our data. Variant chr2-71660631-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 285343.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DYSF | NM_001130987.2 | c.4983G>T | p.Thr1661Thr | synonymous_variant | 45/56 | ENST00000410020.8 | NP_001124459.1 | |
| DYSF | NM_003494.4 | c.4866G>T | p.Thr1622Thr | synonymous_variant | 44/55 | ENST00000258104.8 | NP_003485.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DYSF | ENST00000410020.8 | c.4983G>T | p.Thr1661Thr | synonymous_variant | 45/56 | 1 | NM_001130987.2 | ENSP00000386881.3 | ||
| DYSF | ENST00000258104.8 | c.4866G>T | p.Thr1622Thr | synonymous_variant | 44/55 | 1 | NM_003494.4 | ENSP00000258104.3 |
Frequencies
GnomAD3 genomes 0.000164 AC: 25AN: 152218Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000183 AC: 46AN: 251392Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135856
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GnomAD4 exome AF: 0.000205 AC: 300AN: 1461718Hom.: 0 Cov.: 31 AF XY: 0.000182 AC XY: 132AN XY: 727156
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GnomAD4 genome 0.000164 AC: 25AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74486
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2
| Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 05, 2016 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 29, 2023 | - - |
DYSF-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 03, 2022 | 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). - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Benign:1
| Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 07, 2020 | - - |
Qualitative or quantitative defects of dysferlin Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at