ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.2922T>G (p.Asp974Glu) (rs147674615)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000712265 SCV000226265 uncertain significance not provided 2014-12-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000334797 SCV000373815 uncertain significance Spinal muscular atrophy, distal, autosomal recessive, 1 2017-04-27 criteria provided, single submitter clinical testing The IGHMBP2 c.2922T>G (p.Asp974Glu) missense variant has been reported in one study in which it is found in a compound heterozygous state in one individual with spinal muscular atrophy (Grohmann et al. 2003). Control data are unavailable for this variant, which it is reported at a frequency of 0.00163 in the European American population of the Exome Sequencing Project. The evidence for this variant is limited. The p.Asp974Glu variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for spinal muscular atrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000712265 SCV000642357 likely benign not provided 2019-02-15 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000712265 SCV000842711 uncertain significance not provided 2017-10-17 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000712265 SCV000884027 uncertain significance not provided 2018-04-26 criteria provided, single submitter clinical testing The p.Asp974Glu variant (rs147674615) was reported in one patient with spinal muscular atrophy who carried a second in-frame deletion variant in IGHMBP2 (Grohmann 2003). This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.2 percent in the European Non-Finnish population (identified on 229 out of 124,638 chromosomes, including 1 homozygote) and has been reported to the ClinVar database (Variation ID: 194494). The aspartic acid at position 974 is moderately conserved considering 11 species (Alamut v2.11) and computational analyses of the effects of the p.Asp974Glu variant on protein structure and function provide conflicting results (SIFT: tolerated, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Asp974Glu variant with certainty.

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