Submissions for variant NM_001318852.2(MAPK8IP3):c.2572G>A (p.Val858Met)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002744210	SCV003743256	uncertain significance	Inborn genetic diseases	2021-06-29	criteria provided, single submitter	clinical testing	The c.2569G>A (p.V857M) alteration is located in exon 21 (coding exon 21) of the MAPK8IP3 gene. This alteration results from a G to A substitution at nucleotide position 2569, causing the valine (V) at amino acid position 857 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003994517	SCV004813081	uncertain significance	not specified	2024-02-27	criteria provided, single submitter	clinical testing	Variant summary: MAPK8IP3 c.2569G>A (p.Val857Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.7e-05 in 1612774 control chromosomes. This frequency does not allow for any conclusion about variant significance. There are many heterozygotes reported in gnomAD, and Neurodevelopmental Disorder With Or Without Variable Brain Abnormalities; NEDBA is expected to result in poor or absent speech, supporting a benign role for this variant. Given the variable severity of all other phenotypes associated with this condition, however, the variant cannot be unequivocally classified on the benign spectrum at this time. To our knowledge, no occurrence of c.2569G>A in individuals affected with Neurodevelopmental Disorder With Or Without Variable Brain Abnormalities; NEDBA and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2398173). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
PreventionGenetics, part of Exact Sciences	RCV003985877	SCV004708882	likely benign	MAPK8IP3-related disorder	2023-05-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).