Submissions for variant NM_001369268.1(ACAN):c.7189G>A (p.Val2397Ile)

gnomAD frequency: 0.00088  dbSNP: rs150555123

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514525	SCV000610744	likely benign	not provided	2017-04-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000514525	SCV000856331	uncertain significance	not provided	2017-08-31	criteria provided, single submitter	clinical testing
Invitae	RCV000514525	SCV001035586	likely benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002527434	SCV003544984	uncertain significance	Inborn genetic diseases	2021-08-12	criteria provided, single submitter	clinical testing	The c.7075G>A (p.V2359I) alteration is located in exon 14 (coding exon 13) of the ACAN gene. This alteration results from a G to A substitution at nucleotide position 7075, causing the valine (V) at amino acid position 2359 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235262	SCV003934781	likely benign	not specified	2023-05-04	criteria provided, single submitter	clinical testing	Variant summary: ACAN c.7189G>A (p.Val2397Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00074 in 247260 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 1184 fold of the estimated maximal expected allele frequency for a pathogenic variant in ACAN causing ACAN-Related Disorders phenotype (6.3e-07), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.7189G>A in individuals affected with ACAN-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance (n=2) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000514525	SCV004137585	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	ACAN: BP4