Submissions for variant NM_001098.3(ACO2):c.2338_2339del (p.Gln780fs)

dbSNP: rs1114167284

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000491582	SCV005398300	likely pathogenic	Infantile cerebellar-retinal degeneration	2024-10-08	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with optic atrophy 9 (MIM#616289) and infantile cerebellar-retinal degeneration (MIM#614559). (I) 0108 - This gene is associated with both recessive and dominant disease. Infantile cerebellar-retinal degeneration (MIM#614559) is associated with autosomal recessive inheritance, while optic atrophy 9 (MIM#616289) is associated with both autosomal recessive and dominant inheritance. There is currently no genotype-phenotype correlation between the two conditions, however, autosomal recessive optic atrophy has been shown to be more severe than autosomal dominant optic atrophy (PMID: 34056600). (I) 0208 - Variant is predicted to result in an elongated protein. (SP) 0252 - This variant is homozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0705 - No comparable extension variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been reported as homozygous in three individuals (two of whom are siblings) with clinical features including seizures, microcephaly and neurodevelopmental delay (PMIDs: 32519519, 27435318). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000491582	SCV000282190	pathogenic	Infantile cerebellar-retinal degeneration	2016-01-10	no assertion criteria provided	research
OMIM	RCV000491582	SCV001432778	pathogenic	Infantile cerebellar-retinal degeneration	2020-09-16	no assertion criteria provided	literature only