chr2-71553135-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM1BP4_StrongBP6BS2
The NM_001130987.2(DYSF):āc.1931T>Cā(p.Met644Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,614,058 control chromosomes in the GnomAD database, including 8 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. M644I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.1931T>C | p.Met644Thr | missense_variant | 20/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.1877T>C | p.Met626Thr | missense_variant | 20/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.1931T>C | p.Met644Thr | missense_variant | 20/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.1877T>C | p.Met626Thr | missense_variant | 20/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00112 AC: 170AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00128 AC: 323AN: 251362Hom.: 3 AF XY: 0.00130 AC XY: 176AN XY: 135882
GnomAD4 exome AF: 0.00188 AC: 2751AN: 1461742Hom.: 8 Cov.: 34 AF XY: 0.00182 AC XY: 1324AN XY: 727164
GnomAD4 genome AF: 0.00112 AC: 170AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.000913 AC XY: 68AN XY: 74488
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 06, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 01, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | DYSF: BP4, BS2 - |
Qualitative or quantitative defects of dysferlin Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Miyoshi muscular dystrophy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 22, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 22, 2017 | - - |
DYSF-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 10, 2020 | 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