Submissions for variant NM_173076.3(ABCA12):c.2945A>C (p.Lys982Thr)

gnomAD frequency: 0.00037  dbSNP: rs142196906

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000372818	SCV000427290	uncertain significance	Congenital ichthyosis of skin	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000427740	SCV000536441	uncertain significance	not provided	2017-01-11	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the ABCA12 gene. To our knowledge, the K982T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant. It was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. K982T is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000427740	SCV001055063	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004021797	SCV004857813	uncertain significance	Inborn genetic diseases	2021-07-14	criteria provided, single submitter	clinical testing	The c.2945A>C (p.K982T) alteration is located in exon 22 (coding exon 22) of the ABCA12 gene. This alteration results from a A to C substitution at nucleotide position 2945, causing the lysine (K) at amino acid position 982 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.