rs147678255
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001130987.2(DYSF):c.5276G>A(p.Arg1759His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000323 in 1,614,172 control chromosomes in the GnomAD database, including 1 homozygotes. 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1759C) has been classified as Likely benign.
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.5276G>A | p.Arg1759His | missense_variant | 47/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.5159G>A | p.Arg1720His | missense_variant | 46/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.5276G>A | p.Arg1759His | missense_variant | 47/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.5159G>A | p.Arg1720His | missense_variant | 46/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251454Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135900
GnomAD4 exome AF: 0.000341 AC: 498AN: 1461872Hom.: 1 Cov.: 32 AF XY: 0.000298 AC XY: 217AN XY: 727238
GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:5
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 26, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 26, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 13, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 24, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 01, 2015 | - - |
Qualitative or quantitative defects of dysferlin Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2023 | The c.5159G>A (p.R1720H) alteration is located in exon 46 (coding exon 46) of the DYSF gene. This alteration results from a G to A substitution at nucleotide position 5159, causing the arginine (R) at amino acid position 1720 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 17, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at