ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.2499dup (p.Lys834Ter)

gnomAD frequency: 0.00002  dbSNP: rs767527819
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483202 SCV000572879 likely pathogenic not provided 2017-01-31 criteria provided, single submitter clinical testing A novel c.2499dupT variant that is likely pathogenic has been identified in the IKBKAP gene. The c.2499dupT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2499dupT variant causes a frameshift starting with codon Lysine 834 and changes this amino acid to a premature Stop codon, denoted p.Lys834Ter. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the c.2499dupT variant is not observed with any significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000483202 SCV000932998 pathogenic not provided 2024-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys834*) in the ELP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ELP1 are known to be pathogenic (PMID: 18303054, 24173031). This variant is present in population databases (rs767527819, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ELP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 423215). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000793636 SCV001752800 pathogenic Familial dysautonomia 2021-06-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV003168972 SCV003895125 pathogenic Inborn genetic diseases 2023-02-10 criteria provided, single submitter clinical testing The c.2499dupT (p.K834*) alteration, located in exon 23 (coding exon 22) of the IKBKAP gene, consists of a duplication of T at position 2499. This changes the amino acid from a lysine (K) to a stop codon at amino acid position 834. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the TT allele has an overall frequency of 0.002% (5/251338) total alleles studied. The highest observed frequency was 0.004% (5/113630) of European (non-Finnish) alleles. Based on the available evidence, this alteration is classified as pathogenic.
Counsyl RCV000793636 SCV001132233 likely pathogenic Familial dysautonomia 2017-05-15 no assertion criteria provided clinical testing

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