ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1909-12_1909-11del (rs372662724)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000281629 SCV000457055 uncertain significance Mitochondrial complex II deficiency, nuclear type 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000337728 SCV000457056 uncertain significance Leigh syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000394391 SCV000457057 uncertain significance Pheochromocytoma 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000483037 SCV000566911 likely benign not specified 2017-12-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000492532 SCV000581184 likely benign Hereditary cancer-predisposing syndrome 2013-12-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354980 SCV001549724 likely benign not provided no assertion criteria provided clinical testing The SDHA c.1765-12_1765-11delCT variant was not identified in the literature, however the variant was identified in dbSNP (ID: rs886060516) as “With Uncertain significance allele”. In ClinVar, there were five submissions with conflicting interpretations of pathogenicity under the alias c.1909-12_1909-11delCT (NM_004168.3): likely benign (GeneDx and Ambry Genetics) and uncertain significance (3 submissions from Illumina). The associated conditions are: Pheochromocytoma, Leigh syndrome, Mitochondrial complex II deficiency, and Hereditary cancer-predisposing syndrome. The variant was also identified in LOVD 3.0 (benign), however it was not identified in the Cosmic or MutDB databases. The variant was identified in control databases in 34 of 279302 chromosomes at a frequency of 0.000122 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 9 of 24098 chromosomes (freq: 0.000374), Other in 2 of 7122 chromosomes (freq: 0.000281), European (Finnish) in 6 of 24800 chromosomes (freq: 0.000242), Ashkenazi Jewish in 1 of 10342 chromosomes (freq: 0.000097), European (non-Finnish) in 12 of 127414 chromosomes (freq: 0.000094), Latino in 3 of 35228 chromosomes (freq: 0.000085) and East Asian in 1 of 19696 chromosomes (freq: 0.000051), while the variant was not observed in the South Asian population. All four in silico splicing prediction programs (SpliceSiteFinder-like, MaxEntScan, NNSPLICE, and GeneSplicer) do not predict an impact on splicing and MutationTaster has predicted the variant to be a polymorphism. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000483037 SCV001743715 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000483037 SCV001808888 benign not specified no assertion criteria provided clinical testing

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