rs369017141
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_004006.3(DMD):c.2260G>T(p.Gly754Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000256 in 1,208,698 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts 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. G754V) has been classified as Likely benign.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.2260G>T | p.Gly754Cys | missense_variant | 18/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.2260G>T | p.Gly754Cys | missense_variant | 18/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000134 AC: 15AN: 111557Hom.: 0 Cov.: 23 AF XY: 0.000148 AC XY: 5AN XY: 33759
GnomAD3 exomes AF: 0.0000327 AC: 6AN: 183225Hom.: 0 AF XY: 0.0000443 AC XY: 3AN XY: 67729
GnomAD4 exome AF: 0.0000146 AC: 16AN: 1097141Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 4AN XY: 362559
GnomAD4 genome ? AF: 0.000134 AC: 15AN: 111557Hom.: 0 Cov.: 23 AF XY: 0.000148 AC XY: 5AN XY: 33759
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2023 | The p.G754C variant (also known as c.2260G>T), located in coding exon 18 of the DMD gene, results from a G to T substitution at nucleotide position 2260. The glycine at codon 754 is replaced by cysteine, an amino acid with highly dissimilar properties. Based on data from gnomAD, the T allele has an overall frequency of 0.005% (10/205082) total alleles studied, with 4 hemizygotes observed. The highest observed frequency was 0.047% (9/19042) of African/ African American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Duchenne muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at