ClinVar Miner

Submissions for variant NM_004006.2(DMD):c.10262+1G>A (rs145603325)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723512 SCV000112320 uncertain significance not provided 2018-01-15 criteria provided, single submitter clinical testing
GeneDx RCV000723512 SCV000564939 uncertain significance not provided 2018-03-22 criteria provided, single submitter clinical testing The c.10262+1 G>A variant in the DMD gene has been reported previously in one male individual with autism (Lim et al., 2013), and in one individual with a suspected diagnosis of Duchenne/Becker muscular dystrophy (Kim et al., 2016); however, the clinical information provided in both cases was limited. This splice site variant destroys the canonical splice donor site in intron 71. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. However, the c.10262+1 G>A variant is observed in 14/7337 (0.2%) alleles from individuals of African background, including 2 hemizygous individuals (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, this variant has been observed in the hemizygous state in 5 unaffected individuals undergoing testing at GeneDx. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000990563 SCV000625826 benign Duchenne muscular dystrophy 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621654 SCV000737260 likely benign Cardiovascular phenotype 2019-01-09 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Clinical Services Laboratory,Illumina RCV000778896 SCV000915301 uncertain significance Dilated cardiomyopathy 3B 2018-11-16 criteria provided, single submitter clinical testing The DMD c.10262+1G>A variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. The variant is reported in one study and found in one deceased individual affected with sudden unexpected death (Schieper et al. 2018). Control data are unavailable for this variant, which is reported at a frequency of 0.001630 in the African population of the Genome Aggregation Database and includes nine hemizygotes in this population and 15 hemizygotes in the Total population. Based on the potential impact of splice donor variants and the limited evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for X-linked dilated cardiomyopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Mendelics RCV000990563 SCV001141576 likely benign Duchenne muscular dystrophy 2019-05-28 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000723512 SCV001143740 benign not provided 2019-06-27 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196041 SCV001366470 uncertain significance Primary dilated cardiomyopathy; Malignant tumor of prostate; Cataract (disease); Muscle weakness; Impaired vibration sensation in the lower limbs; Difficulty walking; Hand tremor; Positive Romberg sign; Kyphosis; Muscle cramps; EMG: neuropathic changes; Sensory impairment; EMG: axonal abnormality; Limb fasciculations; Nonprogressive muscular atrophy 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3,PP4. This variant was detected in heterozygous state.

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