rs199588981
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2
The NM_004006.3(DMD):āc.2291A>Gā(p.Asn764Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000196 in 1,209,195 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 87 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. 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. N764K) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.2291A>G | p.Asn764Ser | missense_variant, splice_region_variant | 18/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.2291A>G | p.Asn764Ser | missense_variant, splice_region_variant | 18/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000206 AC: 23AN: 111860Hom.: 0 Cov.: 22 AF XY: 0.000323 AC XY: 11AN XY: 34020
GnomAD3 exomes AF: 0.000371 AC: 68AN: 183211Hom.: 0 AF XY: 0.000310 AC XY: 21AN XY: 67717
GnomAD4 exome AF: 0.000195 AC: 214AN: 1097282Hom.: 0 Cov.: 29 AF XY: 0.000210 AC XY: 76AN XY: 362712
GnomAD4 genome AF: 0.000206 AC: 23AN: 111913Hom.: 0 Cov.: 22 AF XY: 0.000323 AC XY: 11AN XY: 34083
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 04, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 03, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | DMD: PP3, BS2 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Jan 23, 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. | Aug 02, 2019 | - - |
Duchenne muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2021 | This alteration is classified as 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at