ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.455G>A (p.Arg152Gln) (rs62646862)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408574 SCV000281808 likely pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000402682 SCV000337021 likely benign not specified 2015-12-21 criteria provided, single submitter clinical testing
GeneDx RCV000085654 SCV000511880 likely benign not provided 2020-02-27 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 11702214, 23143460, 22264887, 11385708, 26593885, 14517951, 15192030, 25444351, 28118664, 22328824, 15161829, 10958763, 23953153, 16917483, 26764160, 28898540, 29925512, 30093795, 31456290)
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283336 SCV000602336 likely benign none provided 2020-04-30 criteria provided, single submitter clinical testing
Invitae RCV000085654 SCV001118883 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085654 SCV001147343 uncertain significance not provided 2019-02-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001100156 SCV001256662 uncertain significance ABCA4-Related Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ocular Genomics Institute, Massachusetts Eye and Ear RCV000408574 SCV001573368 uncertain significance Stargardt disease 1 2021-04-08 criteria provided, single submitter research The ABCA4 c.455G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: BS1, PP3. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Retina International RCV000085654 SCV000117794 not provided not provided no assertion provided not provided
GenomeConnect, ClinGen RCV000844929 SCV000986745 not provided Stargardt disease no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 06-25-2018 by Lab or GTR ID 239772. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Sharon lab,Hadassah-Hebrew University Medical Center RCV000844929 SCV001160870 likely pathogenic Stargardt disease 2019-06-23 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000085654 SCV001549745 likely benign not provided no assertion criteria provided clinical testing The ABCA4 p.Arg152Gln variant was identified in 5 of 958 proband chromosomes (frequency: 0.005) from individuals or families with Stargardt Disease and Age-related Macular Degeneration and was present in 3 of 440 control chromosomes (frequency: 0.0068) from healthy individuals (Rivera_2000_PMID:10958763; Schulz_2017_PMID:28118664). The variant was also identified in dbSNP (ID: rs62646862), LOVD 3.0 and in ClinVar (classified as likely benign by EGL Genetics, GeneDx and ARUP Laboratories and as likely pathogenic by the University Regensberg Institute of Human Genetics). The variant was not identified in Cosmic. The variant was identified in control databases in 651 of 251232 chromosomes (2 homozygous) at a frequency of 0.002591 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: European (non-Finnish) in 420 of 113574 chromosomes (freq: 0.003698), South Asian in 96 of 30610 chromosomes (freq: 0.003136), Other in 18 of 6136 chromosomes (freq: 0.002934), Latino in 86 of 34578 chromosomes (freq: 0.002487), African in 14 of 16230 chromosomes (freq: 0.000863) and European (Finnish) in 17 of 21646 chromosomes (freq: 0.000785); it was not observed in the Ashkenazi Jewish and East Asian populations. The p.Arg152 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM) 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.

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