rs187926894
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The ENST00000357033.9(DMD):c.2575A>T(p.Thr859Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,209,203 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 54 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
ENST00000357033.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.2575A>T | p.Thr859Ser | missense_variant | 20/79 | ENST00000357033.9 | NP_003997.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.2575A>T | p.Thr859Ser | missense_variant | 20/79 | 1 | NM_004006.3 | ENSP00000354923 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000153 AC: 17AN: 111320Hom.: 0 Cov.: 24 AF XY: 0.000179 AC XY: 6AN XY: 33574
GnomAD3 exomes AF: 0.000114 AC: 21AN: 183485Hom.: 0 AF XY: 0.000132 AC XY: 9AN XY: 67925
GnomAD4 exome AF: 0.000117 AC: 128AN: 1097825Hom.: 0 Cov.: 30 AF XY: 0.000132 AC XY: 48AN XY: 363185
GnomAD4 genome AF: 0.000153 AC: 17AN: 111378Hom.: 0 Cov.: 24 AF XY: 0.000178 AC XY: 6AN XY: 33642
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 25, 2019 | Variant summary: DMD c.2575A>T (p.Thr859Ser) results in a conservative amino acid change located in a spectrin repeat (IPR002017) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 200325 control chromosomes (gnomAD), including 10 hemizygotes. The observed variant frequency is significantly higher than expected for a pathogenic variant in DMD causing Dystrophinopathy phenotype, strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.2575A>T in individuals affected with Dystrophinopathies and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign (3x) and once as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 18, 2017 | - - |
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 24, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 08, 2019 | This variant is associated with the following publications: (PMID: 30564623) - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Duchenne muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 20, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at