rs2273697
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000392.5(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 0.199 in 1,613,940 control chromosomes in the GnomAD database, including 32,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 Likely benign.
Frequency
Consequence
NM_000392.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC2 | NM_000392.5 | c.1249G>A | p.Val417Ile | missense_variant | 10/32 | ENST00000647814.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC2 | ENST00000647814.1 | c.1249G>A | p.Val417Ile | missense_variant | 10/32 | NM_000392.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.186 AC: 28258AN: 152000Hom.: 2734 Cov.: 32
GnomAD3 exomes AF: 0.191 AC: 47979AN: 251224Hom.: 4877 AF XY: 0.197 AC XY: 26739AN XY: 135788
GnomAD4 exome AF: 0.200 AC: 292615AN: 1461822Hom.: 29948 Cov.: 34 AF XY: 0.203 AC XY: 147754AN XY: 727206
GnomAD4 genome ? AF: 0.186 AC: 28256AN: 152118Hom.: 2730 Cov.: 32 AF XY: 0.182 AC XY: 13569AN XY: 74392
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | This variant is associated with the following publications: (PMID: 25087612, 22318656, 21691255, 15821043) - |
Dubin-Johnson syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 08, 2018 | - - |
ABCC2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 16, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at