ClinVar Miner

Submissions for variant NM_002180.3(IGHMBP2):c.1064C>T (p.Ala355Val)

gnomAD frequency: 0.00231  dbSNP: rs142062146
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001087969 SCV000642294 likely benign Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S 2024-01-31 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000727033 SCV000705058 uncertain significance not provided 2017-01-26 criteria provided, single submitter clinical testing
GeneDx RCV000727033 SCV000728569 likely benign not provided 2021-02-22 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000727033 SCV001148360 likely benign not provided 2022-06-01 criteria provided, single submitter clinical testing IGHMBP2: BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000727033 SCV001159710 uncertain significance not provided 2023-10-16 criteria provided, single submitter clinical testing The IGHMBP2 c.1064C>T; p.Ala355Val variant (rs142062146), to our knowledge, is not reported in an individual with neuronopathy or CMT but is reported in the literature in the homozygous state in an individual who was affected with schizophrenia/schizoaffective disorder; however, the contribution of this variant to the phenotype is not known (Need 2012). This variant is reported in ClinVar (Variation ID: 466572) and is found in the African population with an overall allele frequency of 0.76% (189/24,948 alleles) in the Genome Aggregation Database. The alanine at codon 355 is highly conserved but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.585). Although there is no evidence for pathogenicity, we cannot rule out the possibility, therefore, the significance of the variant is uncertain at this time. REFERENCE Need et al. Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia. Am J Hum Genet. 2012 Aug 10;91(2):303-12.
Illumina Laboratory Services, Illumina RCV001109641 SCV001267002 likely benign Autosomal recessive distal spinal muscular atrophy 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Molecular Genetics Laboratory, London Health Sciences Centre RCV001174193 SCV001337319 likely benign Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Ambry Genetics RCV002413540 SCV002716443 likely benign Inborn genetic diseases 2019-11-27 criteria provided, single submitter clinical testing 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.
PreventionGenetics, part of Exact Sciences RCV004553226 SCV004743780 benign IGHMBP2-related disorder 2020-02-05 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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