rs141261536
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The ENST00000357033.9(DMD):āc.5548A>Gā(p.Lys1850Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000232 in 1,207,733 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 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).
Frequency
Genomes: š 0.000081 ( 0 hom., 5 hem., cov: 22)
Exomes š: 0.000017 ( 0 hom. 6 hem. )
Consequence
DMD
ENST00000357033.9 missense
ENST00000357033.9 missense
Scores
3
4
9
Clinical Significance
Conservation
PhyloP100: 6.95
Genes affected
DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.35542512).
BP6
Variant X-32345981-T-C is Benign according to our data. Variant chrX-32345981-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197077.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2}.
BS2
High Hemizygotes in GnomAd4 at 5 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.5548A>G | p.Lys1850Glu | missense_variant | 39/79 | ENST00000357033.9 | NP_003997.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.5548A>G | p.Lys1850Glu | missense_variant | 39/79 | 1 | NM_004006.3 | ENSP00000354923 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000810 AC: 9AN: 111089Hom.: 0 Cov.: 22 AF XY: 0.000150 AC XY: 5AN XY: 33327
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GnomAD3 exomes AF: 0.0000164 AC: 3AN: 182421Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67237
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GnomAD4 exome AF: 0.0000173 AC: 19AN: 1096644Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 6AN XY: 362660
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GnomAD4 genome AF: 0.0000810 AC: 9AN: 111089Hom.: 0 Cov.: 22 AF XY: 0.000150 AC XY: 5AN XY: 33327
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 20, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 03, 2015 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 08, 2021 | The p.K1850E variant (also known as c.5548A>G), located in coding exon 39 of the DMD gene, results from an A to G substitution at nucleotide position 5548. The lysine at codon 1850 is replaced by glutamic acid, an amino acid with similar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.002% (5/204076) total alleles studied, including one hemizygote. The highest observed frequency was 0.02% (4/18957) 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
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 04, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D;.;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;.;N;D
REVEL
Uncertain
Sift
Benign
.;T;.;T;D
Sift4G
Benign
T;T;T;T;D
Polyphen
1.0
.;D;.;.;.
Vest4
MVP
MPC
0.045
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at