rs148858485
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001130987.2(DYSF):āc.3678C>Gā(p.Ile1226Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000802 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I1226I) has been classified as Likely benign.
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.3678C>G | p.Ile1226Met | missense_variant | 33/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.3624C>G | p.Ile1208Met | missense_variant | 33/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.3678C>G | p.Ile1226Met | missense_variant | 33/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.3624C>G | p.Ile1208Met | missense_variant | 33/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000677 AC: 103AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000696 AC: 175AN: 251294Hom.: 0 AF XY: 0.000640 AC XY: 87AN XY: 135854
GnomAD4 exome AF: 0.000815 AC: 1192AN: 1461778Hom.: 1 Cov.: 32 AF XY: 0.000770 AC XY: 560AN XY: 727182
GnomAD4 genome ? AF: 0.000676 AC: 103AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40AN XY: 74494
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 13, 2018 | This variant is associated with the following publications: (PMID: 26764160, 16010686, 25900324, 32528171) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 13, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 27, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 14, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | DYSF: BP4 - |
Qualitative or quantitative defects of dysferlin Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 06, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at