ClinVar Miner

Submissions for variant NM_017780.4(CHD7):c.8366C>T (p.Ala2789Val)

gnomAD frequency: 0.00019  dbSNP: rs376934539
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000177945 SCV000229908 uncertain significance not provided 2014-07-07 criteria provided, single submitter clinical testing
Invitae RCV000796515 SCV000936033 uncertain significance CHARGE association 2021-08-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000177945 SCV001552410 likely benign not provided no assertion criteria provided clinical testing The CHD7 p.Ala2789Val variant was identified in 1 of 438 proband chromosomes (frequency: 0.0023) from individuals or families with Kallmann Syndrome (Costa-Barbosa_2013_PMID:23533228). The variant was identified in dbSNP (ID: rs376934539) and ClinVar (classified as uncertain significance by Invitae and EGL Genetics). The variant was identified in control databases in 25 of 274676 chromosomes at a frequency of 0.00009102 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Other in 4 of 7010 chromosomes (freq: 0.000571), African in 11 of 23378 chromosomes (freq: 0.000471), European (non-Finnish) in 8 of 125762 chromosomes (freq: 0.000064), European (Finnish) in 1 of 24348 chromosomes (freq: 0.000041) and South Asian in 1 of 29956 chromosomes (freq: 0.000033), but was not observed in the Latino, Ashkenazi Jewish, or East Asian populations. The p.Ala2789 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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 RCV000177945 SCV001744015 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000177945 SCV001964355 likely benign not provided no assertion criteria provided clinical testing

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