Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000392(ABCC2):c.1249G>A(p.Val417Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152000 control chromosomes in the gnomAD Genomes database, including 2734 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V417A) has been classified as Uncertain significance.
Verdict is Benign. Variant got -20 ACMG points.
GnomAD3 genomes AF: 0.186AC: 28258AN: 152000Hom.: 2734Cov.: 32 GnomAD3 exomes AF: 0.191AC: 47979AN: 251224Hom.: 4877 AF XY: 0.197AC XY: 26739AN XY: 135788 GnomAD4 exome AF: 0.200AC: 292615AN: 1461822Hom.: 29948 AF XY: 0.203AC XY: 147754AN XY: 727206
Submissions by phenotype
|Benign, criteria provided, single submitter||clinical testing||Eurofins Ntd Llc (ga)||May 08, 2018||- -|
|Benign, criteria provided, single submitter||clinical testing||PreventionGenetics, PreventionGenetics||-||- -|
|Benign, criteria provided, single submitter||clinical testing||Invitae||Oct 30, 2022||- -|
|Benign, criteria provided, single submitter||clinical testing||GeneDx||Nov 10, 2018||This variant is associated with the following publications: (PMID: 25087612, 22318656, 21691255, 15821043) -|
|Benign, criteria provided, single submitter||clinical testing||Illumina Laboratory Services, Illumina||Mar 06, 2018||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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -|
|Benign, criteria provided, single submitter||clinical testing||Genome-Nilou Lab||Jul 14, 2021||- -|
Find out detailed SpliceAI scores and Pangolin per-transcript scores at